Anti-tumor effect and its related mechanisms of cinobufotalin combined with cisplatin on H22 liver cancer mice / 中国中药杂志

In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.

Effects of Total Glucosides of Paeonia lactiflora Combined with Cisplatin on Tumor Inhibition and Renal Injury Improvement in Model Rats with Gastric Cancer / 中国药房

OBJECTIVE：To study the improvement effects of total glucosides of Paeonia l actiflora（TGPL）combined with cisplatin on tumor inhibition and renal injury in gastric cancer model rats. METHODS ：Totally 75 rats were divided into control group（normal saline ，i.g.），model group （normal saline ，i.g.），cisplatin group （25 mg/kg，i.p.），TGPL group （200 mg/kg，i.g.）， TGPL+cisplatin group （200 mg/kg TGPL ，i.g.+25 mg/kg cisplatin ，i.p.），with 15 rats in each group. Except for control group ， gastric cancer rat models were established in other groups by subcutaneous inoculation of gastric cancer BGC 823 cell suspension. After modeling ，they were given relevant medicine intraperitoneally/intragastrically ，for consecutive 28 d. The tumor weight and tumor inhibition rate were measured. The apoptosis rate in tumor tissue was detected by flow cytometry ；Western blotting assay was used to detect the levels of Bcl- 2 and Bax in tumor tissue ；ELISA or biochemical analyzer were used to determine the levels of IL-18 and KIM- 1 in urine ，BUN and Scr in serum ，as well as SOD， MDA and GSH in renal tissue ； histopathological 015）changes of renal tissue in rats were detected by HE staining. 65896961。E-mail：taolitianxia999@163.com RESULTS： Compared with control group ， there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine，serum levels of BUN and Scr ，the levels of SOD MDA and GSH in renal tissue of model group （P＞0.05）；no obvious histopathological change was found in renal tissue. Compared with model group ，tumor weight in cisplatin group was decreased significantly ，while cell apoptosis was increased significantly，while expression level of Bax in tumor tissue was increased significantly ，the expression level of Bcl- 2 was decreased significantly（P＜0.05）；the levels of IL- 18 and KIM- 1 in urine ，BUN and Scr in serum and MDA in kidney were increased significantly（P＜0.05）；the levels of SOD and GSH in renal tissue were decreased significantly （P＜0.05）；renal tubules were dilated，vacuoles of epithelial cells in basal layer and cast in renal tubules formed . Compared with cisplatin ，tumor weight in TGPL+cisplatin group was decreased significantly ，while apoptotic rate was increased significantly ，while the level of Bax was increased significantly ，expression level of Bcl- 2 was decreased significantly （P＜0.05）；the levels of IL- 18 and KIM- 1 in urine ， BUN and Scr in serum and MDA in renal tissue were significantly reduced （P＜0.05）；the levels of SOD and GSH in renal tissue were increased significantly （P＜0.05）；there was no tubule dilation ，but vacuoles were occasionally found in basal epithelial cells，and the cast formation in renal tubules was rare. Compared with TGPL group，tumor weight in TGPL +cisplatin group was significantly reduced ，the tumor inhibition rate was significantly increased ，the apoptosis rate was significantly increased ，while the expression level of Bax in tumor tissue was increased significantly ，expression level of Bcl- 2 was decreased significantly （P＜ 0.05）；there was no statistical significance in the levels of IL- 18 and KIM- 1 in urine ，the levels of BUN and Scr in serum ，the levels of SOD ，MDA and GSH in renal tissue （P＞0.05）；a small amount of inflammatory cells infiltrated occasionally in renal tissue. CONCLUSIONS ：TGPL combined with cisplatin can inhibit tumor growth ，promote tumor cell apoptosis and improve renal injury induced by cisplatin.

Effect of Astragalus Polysaccharide on Growth and Tumor-related Apoptosis Protein of Human Breast Cancer MDA-MB-231 Transplanted Tumor in Nude Mice / 中国实验方剂学杂志

Objective: To observe the inhibitory effect of astragalus polysaccharides (APS) on growth of human breast cancer MDA-MB-231 xenograft tumor in nude mice and its effect on the apoptosis of tumor cells, in order to study the effect of APS on growth and induction of apoptosis of triple negative breast cancer MDA-MB-231 and its possible molecular mechanism. Method: Human breast cancer cell MDA-MB-231 was inoculated into the right axillary subcutaneous of BALB/c-nu female nude mice to establish the transplanted tumor model of breast cancer. Eighteen nude mice were randomly divided into 3 groups:model group (saline per day), low-dose APS group (200 mg·kg-1 APS per day), and high-dose APS group (400 mg·kg-1 APS per day), with 6 rats in each group. The drug was administered by gavage (200 μL) daily for 21 days. In the experiment, the length and diameter of breast cancer transplanted tumor were measured every two days, and the tumor volume was recorded and calculated. At the end of the experiment, the changes of tumor mass and tumor volume of the low and high-dose APS groups and the model group were observed and compared, and the tumor inhibition rate was calculated. The cell morphology in tumor tissue was observed by hematoxylin-eosin (HE) staining, and Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was used to verify the apoptosis of breast cancer tissues. The expressions of apoptosis-related proteins, such as B-cell lymphoma/leukemia-2 protein (Bcl-2), Bcl-2 associated X protein (Bax), Caspase in tumor tissues was detected by Western blot. Result: The tumor volume of breast cancer decreased in the low and high-dose APS groups, and the tumor inhibition rates were 37.9%and 57.57%, respectively, with statistically significant differences from the model group (PP0.01). HE of tumor tissue cells showed that APS led to obvious morphological changes, with apoptosis in the tissue cells. TUNEL staining showed that the apoptosis rate of tumor cells in APS intervention groups was higher than that in control group. Western blot showed that expression of Bcl-2 protein decreased(PPPPConclusion: APS can effectively inhibit the growth of MDA-MB-231 breast cancer xenografts in nude mice and induce apoptosis in human breast cancer MDA-MB-231 cells. The mechanism may be related to the effect of APS on expressions of apoptosis-related proteins Bcl-2, Bax, Caspase-9 and Caspase-7 in breast cancer cells.

Maspin in tumor formation and progression / 医学研究生学报

Maspin gene is a tumor suppressor that encodes serine protease inhibitor. It was found that maspin could induce apoptosis, inhibit the invasion and metastasis of tumor cells, and suppress angiogenesis. In recent years, maspin has also been found to be associated with host immunity. The review is to summarize structure distribution, tumor inhibition mechanism and immunological correlation of maspin.

Preparation and Antitumor Activity of Etoposide-loaded Solid Lipid Nanoparticles / 中国药师

Objective:To prepare solid lipid nanoparticles of etoposide and evaluate the inhibitory rate against Lewis lung cancer cells in mice. Methods:Etoposide-loaded solid lipid nanoparticles were prepared by a hot melting emulsification and high pressure homogenization method. The physicochemical properties such as the appearance, microstructure, particle size distribution and zeta potential of the solid lipid nanoparticles were studied. The in vitro release behavior of the solid lipid nanoparticles were evaluated. The inhibitory effect of etoposide-loaded solid lipid nanoparticles and etoposide injection on Lewis lung cancer cells was compared. Results:Etoposide-loaded solid lipid nanoparticles showed a light blue transparent liquid,which was uniformly spherical under the transmission electron microscope. The average particle size was (153.2 ± 32.8) nm, PdI was (0.185 ± 0.031),and the zeta potential was(-17.4 ± 1.1) mV. The solid lipid nanoparticles could delay the drug release and 52.4% of the drug was released in 24 h. Etoposide-loaded solid lipid nanoparticles could significantly inhibit the growth of Lewis lung cancer cells in mice. And the inhibitory rate of the solid lipid nanoparticles was significantly higher than that of etoposide injection (P < 0.05). Conclusion:The solid lipid nanoparticles prepared by hot melting emulsification and high pressure homogenization method have good antitumor effect on Lewis lung cancer cells,which can be used as a new drug delivery system for etoposide with certain application prospect in lung cancer treatment.

Effects of Sinomenine on Tumor Suppressor Gene P16 And P53 in Rats with Lung Cancer / 世界科学技术-中医药现代化

This study was aimed to investigate the effect of sinomenine on the expression of tumor suppressor gene P 16 and P53 in rats with lung cancer.A total of 40 male SD rats were treated by left-lung vein injection of WALKER-256 cell suspension to establish transplanted lung cancer model.After 3 weeks,30 rats screened of tumor were randomly divided into the model group,cyclophosphamide (CP) group and the sinomenine treatment group.Another 10 healthy SD rats were set as the normal control group.Sinomenine treatment group was treated with the subcutaneous injection of 10％ sinomenine hydrochloride for 10 weeks.CP was injected in the CP group as positive control.The same amount of normal saline was injected in the normal control group and the model control group.After 10 weeks of treatments,lung tumors of each group were removed to measure the tumor volume and weight.And the tumor inhibition rate was calculated.Then,flow cytometry was used to detect the proportion of WALKER-256 cells in tumor tissues in G1,G2,M and S around four cycles.Immunohistochemistry was adopted to detect positive expression rates of P16 and P53 protein.Reverse transcription polymerase chain reaction (RT-PCR) were used to detect expression of P16mRNA and P53mRNA.The results showed that compared with the model control group,the inhibition rate of sinomenine group was 30.15％;the positive expression rate of P16mRNA and P53mRNA protein were significantly decreased;expressions of P 16mRNA and P53mRNA were lower;tumor volume and tumor weight in S period got down significantly.The rates of cells in G1 and G2 periods got higher (P＜0.05).It was concluded that sinomenine may inhibit the differentiation and proliferation of WALKER-256 transplanted lung cancer cells in rats by regulating the expression of tumor suppressor gene P 16 and P53,regulating the ratio of cells in G1,G2 and S periods.

The synergistic antiproliferative effect of pterostilbene and acetylshikonin on B16 F10 cells / 中国药理学通报

Aim Toevaluatethesynergisticeffectof anti-tumor by the pterostilbene and acetylshikonin act-ing on B16F10 cells and investigate the interrelated mechanisms.Methods Theresearchscreenedandan-alyzed the target-related of pterostilbene and ace-tylshikonin by system-pharmacological methods. The proliferative inhibition rate of B16F10 cells were meas-ured by MTT.The apoptosis in B16F10 cells were proved by both cellular morphological and biochemical methods.The expression of apoptotic genes were as-sessed via RT-PCR.The apoptotic rate and cell cycle were measured by flow cytometry.Melanoma models were established in C57BL/6 mice,and the inhibitory rateoftumorgrowthwasmeasured.Results The14 targets of pterostilbene were closely related to cell cy-cle,acetylshikonin′s 12 targets displayed a relationship with apoptosis,and correlated with p53 signaling path-way.Pterostilbene along with acetylshikonin signifi-cantly inhibited cell proliferation of B16F10 cells in a dose-dependent way and resulted a remarkable syner-gistic effect.The apoptotic rate reached highest with a blocked-cell cycle at G1 phase in the co-treatment group.The RT-PCR results showed that the expres-sions of p53,Bax and p21 were up-regulated and the expressions of Bcl-2,CDK2 and Cyclin E were down-regulated with time.The changes of p53,Bax and Bcl-2 were obvious in combined treated group.All treat-ments in vivo showed different tumor inhibition rates while co-treatment group showed highest.Conclusion Pterostilbenecooperatedwithacetylshikonininhibits the proliferation in B16F10 cells,and activates the p53 signaling pathway to induce the B16F10 cells apoptosis and a cell cycle arrest.

Effects of Salvianolate on the Expression of VEGF and MMP-9 in Lung Tissue of Mice with Lung Cancer / 中国药房

OBJECTIVE:To study the effects of salvianolate on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9(MMP-9)in lung tissue of mice with lung cancer. METHODS:C57BL/6 mice were randomly divid-ed into model group (normal saline),positive control group (cyclophosphamide 50 mg/kg) and salvianolate low-dose,medi-um-dose and high-dose groups(20,40,80 g/kg)with 10 mice in each group. They were ig 1 000 mg/kg urethane,twice a day, for consecutive 4 weeks to establish lung cancer model. After modeling,they were given relevant medicine intragastrically once a day for consecutive 14 d. Mice behaviors,symptoms,body weight,tumor inhibition rate,spleen index,thymus index,and the ex-pressions of VEGF and MMP-9 in lung tissue among groups were compared. RESULTS:The activity of mice in model group disap-peared,dull coat color,preferred crowding together;the above-mentioned phenomenon improved in positive control group and sal-vianolate different dose groups. The body weight of mice in positive control group,salvianolate low-dose group,medium-dose group and high-dose group were(21.01±2.95)g,(20.89±3.14)g,(21.03±3.02)g,(21.24±3.17)g;and the tumor inhibition rates were(41.12±15.42)%,(36.92±10.42)%,(39.41±12.39)% and(37.19±10.39)%;compared with model group,spleen index,thymus index,and the expressions of VEGF (except for positive control group) and MMP-9 in other 4 groups decreased (P<0.05). CONCLUSIONS:Salvianolate shows obvious inhibitory effects on mice with lung cancer,which may be related to in-hibiting expressions of VEGF and MMP-9 in lung tissue.

Study on Targeting of Folic Acid-modified Docetaxel Nano-liposome to Hepatocellular Carcinoma Bel-7402 Cells in vivo and in vitro / 中国药房

OBJECTIVE:To study the targeting of folic acid(FA)-modified docetaxel(DOC)nano-liposome(L-DOC-FA)to hepatocellular carcinoma Bel-7402 cells in vivo and in vitro. METHODS:The cell viability and survival rate of Bel-7402 cells was tested by CCK-8 kit after treated with 0,1,2,5,10 and 20 μg/ml DOC,L-DOC and L-DOC-FA for 24 h. And then,the fluores-cein isothiocyanate was used to label L-DOC and L-DOC-FA nano-liposome,and the rate of L-DOC and L-DOC-FA absorbed by hepatocellular carcinoma Bel-7402 cells were detected. 125I was used to label L-DOC and L-DOC-FA nano-liposome,and then the contents of them in the subcutaneous tumor tissues were detected. 28 Balb/c naked mice were selected and given liver cell suspen-sion via back ih to induce tumor model. After modeling,naked mice were divided into blank control group(normal saline),DOC group(3 mg/kg),L-DOC(3 mg/kg,by DOC)and L-DOC-FA(3 mg/kg,by DOC). They were given relevant medicine intrave-nously once a day for consecutive 30 d. The relative tumor volume in naked mice was detected. RESULTS:DOC,L-DOC and L-DOC-FA all inhibited the cell viability of Bel-7402 cells,the survival rate of cells decreased in concentration-dependant manner;compared with DOC and L-DOC,the cell viability decreased after treated with L-DOC-FA,the survival rate of cells decreased (PL-DOC (31.2%),with statistical significance (P<0.01). The content of L-DOC-FA in tumor was significantly more than that of L-DOC (P<0.01). In addition,3 mg/kg L-DOC-FA showed better inhibitory effect than 3 mg/kg L-DOC and DOC on tumor,and the rela-tive tumor volume was smaller(P<0.01). CONCLUSIONS:L-DOC-FA has obvious targeting to Bel-7402 cells in vivo and in vi-tro,and shows good inhibitory effect on tumor in vivo and in vitro.

Preparation and Tumor Inhibition Effect of Transferrin Modified Paclitaxel-loaded Liposome / 中国药房

OBJECTIVE:To prepare transferrin modified paclitaxel-loaded liposome(TF-PTX-LP),and to study the tumor in-hibition effect. METHODS:TF-PTX-LP was prepared by thin-film method,and morphology of TF-PTX-LP was observed. Qualita-tive and quantitative investigation were used to value the uptake efficiency of TF-LP and LP by HepG2 cells. The proliferation inhi-bition rate of HepG2 cells was investigated after treated with PTX,PTX-LP and TF-PTX-LP for 24,48 and 72 h. Tumor spheres were prepared by using HepG2 cells. Effects of normal saline,PTX,PTX-LP and TF-PTX-LP on the volume of tumor spheres were investigated after 0,1,2,4,5,6 and 7 d treatment. HepG2 tumor-bearing nude mice model was induced. Inhibitory effects of normal saline,PTX,PTX-LP and TF-PTX-LP(8.5 mg/kg by PTX)on transplantable tumor of tumor-bearing nude mice were in-vestigated. RESULTS:TF-PTX-LP showed uniform spherical shape,with particle size of 100-120 nm. The fluorescence intensity of HepG2 cells treated with TF-LP was stronger than that treated with LP(P<0.01). Compared with PTX and PTX-LP,TF-PTX-LP showed higher proliferation inhibition rate(P<0.01). Compared with normal saline,PTX and PTX-LP,tumor spheres were small-er in volume after treated with TF-PTX-LP,and inhibition rate of tumor was higher in tumor-bearing nude mice;there were statisti-cal significance after treated for 6,7 d(P<0.01). The proliferation inhibition rate and tumor spheres volume changed in time-de-pendent manner. CONCLUSIONS:TF-PTX-LP which owns good tumor inhibition effect is prepared successfully.

Introduction of Professor Xie Jianguo's Clinical Experience for Treatment of Advanced Lung Cancer on Survival with Tumor / 浙江中医药大学学报

Objective]This article discussed Professor Xie Jianguo's survival with tumor experience on advanced lung cancer treatment in the last decade. [Methods]To observe Professor Xie Jianguo's survival with tumor experience of advanced lung cancer on the clinical treatment process, and organize related cases, which summarized the unique thoughts of treatment, commonly used empirical prescriptions and demonstrated with typical clinical cases. [Resluts] Professor Xie Jianguo's theoretical guidance on advanced lung cancer treatment, included tumor inhibition, anticancer effect, survival with tumor. Treatment methods, included recruitment of the vital qi, adjusting the internal environment, the phlegm, stasis toxin factors, with rigorous thinking, sophisticated medication. [Conclusion] Professor Xie Jianguo's survival with tumor experience on advanced lung cancer treatment has remarkable significance in guiding clinical treatment.

Synergism and attenuation effects of Scapharca Subcrenata Extraction on NP chemotherapy / 中国比较医学杂志

Objective To investigate the synergism and attenuation effects of Scapharca Subcrenata Extraction on NP chemotherapy in model mice.Methods The models of nude mice were induced with A549 cell line xenograft.The tumor inhibiting rates, body weight, food intake, hematology and blood biochemistry index were determined to evaluate the synergism and attenuation effects of Scapharca Subcrenata Extraction (125、250、500 mg/kg, i.g) on NP chemotherapy. Results Compared with NP chemotherapy group, the tumor inhibiting rates, body weight, food intake, white blood cell number were increased and glutamate pyruvate transaminase, glutamic oxalacetic transaminase and urea nitrogen were decreased markedly in NP chemotherapy plus Scapharca Subcrenata Extraction groups. Conclusion Scapharca Subcrenata Extraction has a remarkable synergism and attenuation effects on NP chemotherapy.

Anti-tumor effect of LTA combined with 5-FU on H22 tumor bearing mice

OBJECTIVE@#To study the effect of lipoteichoic acid (LTA) and 5-FU on the expression of caspase-3, EGFR, TGF-α proteins of tumor tissue of H22 cancer bearing mice and its anti-tumor mechanism.@*METHODS@#A total of 40 SPF grade Kunming mice were selected to establish H22 liver cancer model, and then the mice were divided into 4 groups at random with ten mice in each group. Group A was given saline lavage treatment, Group B was treated with 5-FU by intraperitoneal injection, Group C was treated with LTA by lump body injection; Group D was treated with LTA by lump body injection and 5-FU by intraperitoneal injection. Two weeks after the treatment, the mice in each group were executed and the tumor tissue was stripping and weighted, and the tumor growth inhibition ratio was calculated. Then the tumor tissue was processed for conventional embedding, sectioned to observe the expression of caspase-3, EGFR, TGF-α by immunohistochemical staining method.@*RESULTS@#The tumor inhibitory rate o f Group D was significantly higher than Groups B and C (P  0.05). The IDO values of TGF-α, EGFR proteins in Groups B, C, D mice tumor tissue were significantly lower than that in group A (P < 0.05); while IDO value of caspase-3 in Groups B, C, D group mice tumor tissue was significantly higher than that in Group A (P < 0.05). The IDO value of TGF-α, EGFR in Group D mice tumor tissue were significantly lower than that in Groups B and C; While IDO value of aspase-3 in Group D was significantly higher than that in Groups B and C (P < 0.05).@*CONCLUSIONS@#LTA combined with 5-FU can effectively inhibit the tumorigenesis of H22 tumor bearing mice, increase the caspase-3 protein expression, inhibit TGF-α and EGFR protein expression, further promote tumor cell apoptosis and play a synergistic antitumor effect.

Anti-tumor effect of LTA combined with 5-FU on H22 tumor bearing mice

Objective: To study the effect of lipoteichoic acid (LTA) and 5-FU on the expression of caspase-3, EGFR, TGF-α proteins of tumor tissue of H22 cancer bearing mice and its anti-tumor mechanism. Methods: A total of 40 SPF grade Kunming mice were selected to establish H22 liver cancer model, and then the mice were divided into 4 groups at random with ten mice in each group. Group A was given saline lavage treatment, Group B was treated with 5-FU by intraperitoneal injection, Group C was treated with LTA by lump body injection; Group D was treated with LTA by lump body injection and 5-FU by intraperitoneal injection. Two weeks after the treatment, the mice in each group were executed and the tumor tissue was stripping and weighted, and the tumor growth inhibition ratio was calculated. Then the tumor tissue was processed for conventional embedding, sectioned to observe the expression of caspase-3, EGFR, TGF-α by immunohistochemical staining method. Results: The tumor inhibitory rate o f Group D was significantly higher than Groups B and C (P 0.05). The IDO values of TGF-α, EGFR proteins in Groups B, C, D mice tumor tissue were significantly lower than that in group A (P < 0.05); while IDO value of caspase-3 in Groups B, C, D group mice tumor tissue was significantly higher than that in Group A (P < 0.05). The IDO value of TGF-α, EGFR in Group D mice tumor tissue were significantly lower than that in Groups B and C; While IDO value of aspase-3 in Group D was significantly higher than that in Groups B and C (P < 0.05). Conclusions: LTA combined with 5-FU can effectively inhibit the tumorigenesis of H22 tumor bearing mice, increase the caspase-3 protein expression, inhibit TGF-α and EGFR protein expression, further promote tumor cell apoptosis and play a synergistic antitumor effect.

The Inhibitory Effect of Dendritic Cell Tumor Vaccine Induced by Astragalus Polysaccharides on the Expression of Cytokines Th1/Th2 in S180 Tumor-Bearing Mice / 天津医药

Objective To study the antitumor effects of dendritic cell vaccine induced by astragalus polysaccha?rides on S180 tumor-bearing mice, and its possible mechanism. Methods Dendritic cells derived from mouse bone marrow were induced maturation by astragalus polysaccharides and loaded with S180 tumor antigen to prepare tumor vaccine. Tu?mor-bearing mice were divided into four groups and treated on day-5 and day-10 respectively. Group A was injected with NS, Group B with CTX (50 mg/kg), Group C with dendritic cells induced by astragalus polysaccharides and Group D with dendritic cells induced by tumor necrosis factor (TNF)-α. After 12 days of tumor-bearing, the animals were killed. The sub?cutaneous sarcoma, thymus and spleen were separated and weighted. The inhibitory rate, thymus index and spleen index were then calculated. ELISA assay was used to detect the levels of interleukin (IL)-4, interferon (IFN)-γin serum of tumor bearing mice. Results The tumor inhibition rate was higher in astragalus polysaccharide group and cytokine group than that of CTX group (64.25%, 64.10%vs 35.11%). The thymus index was higher in astragalus polysaccharide group and cyto?kine group than that of CTX group (1.69 ± 0.26, 1.74 ± 0.38 vs 1.45 ± 0.22). The spleen index was higher in astragalus poly?saccharide group and cytokine group than that of CTX group (5.44 ± 0.76, 5.31 ± 0.81 vs 3.54 ± 0.52). The level of IL-4 was lower in astragalus polysaccharide group and cytokine group than that of CTX group (15.66±2.57, 14.72 ± 4.84 vs 23.95 ± 6.07). The level of IFN-γwas higher in astragalus polysaccharide group and cytokine group than that of CTX group (16.54 ± 3.71, 17.20 ± 2.03 vs 10.37 ± 2.19). All the differences were statistically significant (P<0.05). Conclusion Dendritic cell vaccine induced by astragalus polysaccharides can effectively inhibit tumor growth. Its mechanism may be associated with the promotion spleen index and thymus index of S180 tumor-bearing mice, the effective correction of Th1/Th2 imbalance in?duced by tumor, and the enhancement of antitumor immune responses.

Preparation of vinorelbine tartrate liposomes injection by different methods and their properties and antitumor effects / 中国药学杂志

RESULTS: All EEs of the three VLIs were over 93%. The mean diameters, Zeta potentials and entrapment efficiencies of the three VLIs were similar. Meanwhile the three VLIs were stable in the long-term stability test. The cryo-TEM showed that almost all vesicles had spherical structure and uniform nanosize. Furthermore, some colloid substances and acicular crystal were found inside VLI-2 and VLI-3, respectively. The release rate of VLI-3 was slower, which indicated that the drug crystal probably influence the in vitro drug release. The pharmacodynamic test showed that the antitumor effect of VLI-3 was better than VLI-2 and VLI-1, while those of the latter two were superior to VI.

Anti-tumor Effect of Tenacissoside H and Influence on Immune Function of Lewis Lung Cancer Mice / 中国中医药信息杂志

Objective To study the anti-tumor effect of tenacissoside H on Lewis lung cancer mice, and explore its impacts on immune function of tumor-bearing mice. Methods Mice was injected Lewis lung cancer cells subcutaneously to the right axilla. Thirty successful tumor-bearing mice were randomly divided into model group, the cyclophosphamide (CTX) group and tenacissoside H group, 10 mice in each group. Three days after inoculation, mice were intraperitoneally injected by normal saline, CTX and tenacissoside H respectively every two days, 0.2 mL in each mouse. On the 21st day, the eyeballs were extracted and blood was drawn, tumor tissue, spleen and thymus were taken and weighted to calculate tumor inhibition rate, spleen index and thymus index, and the contents of IL-2 and IL-10 were detected by ELISA. Results The tumor weights of CTX group and tenacissoside H group were lower than that of the model group with significant difference (P<0.05), and the tumor inhibition rates were 54.12%, 25.68%. The thymus index and spleen index of tenacissoside H group increased, but that of CTX group decreased significantly. Compared with the model group, the IL-2 level of tenacissoside H group was significantly increased, while the IL-10 level decreased. Conclusion Tenacissoside H can inhibit growth and metastasis of Lewis lung cancer, regulate the expression of IL-2 and IL-10, and improve the immune function of tumor-bearing mice.

Radiosensitizing effect of cisplatin on CNE-1 xenograft in nude mice / 中华放射肿瘤学杂志

Objective To investigate influence of cisplatin (DDP) on the tumor inhibition rate,transcriptional levels of CyclinB1 and CyclinD1 of CNE-1 xenograft in nude mice.Methods Tumor mode of nude mice CNE-1 xenograft was established.Then mice were divided into control arm,DDP arm,high speed irradiation arm,simulated intensity modulated radiation therapy (IMRT) arm and simulated IMRT + DDP arm,with 12 mice in each arm.Irradiation dose was 20 Gy with a single fraction.DDP was 15 μg/g weight.The maximum diameter of tumor base was measured every other day.The growth curve was drawn and tumor inhibition rate werevcalculated after 40 days.The transcriptional level of CyclinB1 and CyclinD1 of xenograft was measured by RT-PCR.The results of different groups were compared with one-factor analysis of variance.Results Tumor inhibition rates of the control arm,DDP arm,high speed irradiation arm,simulated IMRT arm and simulated IMRT + DDP arm were-129.1％,-71.2％,42.5％,35.3％ and 47.1％,respectively.There was significant difference between the high speed irradiation arm and simulated IMRT arm (P =0.034),but not between the high speed irradiation arm and simulated IMRT + DDP arm (P =0.222).The transcriptional levels of CyclinB1 in the arms were 0.429,0.386,0.322,0.354 and 0.268.There were significant differences between the high speed irradiation arm and the simulated IMRT arm or the simulated IMRT + DDP arm (P =0.007 and 0.000).The transcriptional levels of CyclinD1 in the arms were 0.716,0.583,0.348,0.495 and 0.296,respectively.There was significant difference between the acute irradiation arm and the simulated IMRT arm (P =0.000),but there was no significant difference between the high speed irradiation arm and the simulated IMRT + DDP arm (P =0.072).Conclusions Irradiation of 20 Gy single fraction,or combined with DDP are effective on the CNE-1 xenograft in nude mice,but DDP alone can only lower the tumor growth speed.Irradiation of 20 Gy single fraction,or combined with DDP,or DDP alone can reduce the transcriptional levels of CyclinB1 and CyclinD1.As the single therapeutic time is prolonged in IMRT mode,the tumor inhibition rate is reduce,and the reduce of the transcriptional levels of CyclinB1 and CyclinD1 is depressed,while combined DDP can compensate the decline of the biological effect.

Inhibitory effect of 17aα-D-homo-ethynylestradiol-3-acetae combined with irradiation on melanoma B16 growth / 中华放射医学与防护杂志

Objective To investigate the antitumor effect of 17aα-D-homo-ethynylestradiol-3-acetae on the mice transplanted with melanoma (B16) tumor cells,and to explore the possible synergistic effect with irradiation.Methods IRM-2 mice transplanted with B16 cells were randomly classified into control group,irradiation group,17aα-D-homo-ethynylestradiol-3-acetae drug ( high dose,medium dose,low dose) groups,and drug and irradiation combination group.Mice in drug group and the combination group were intraperitoneally injected with 5,7.5,and 10 mg/kg drug for 7 days.Mice in the irradiation and combination group received 1 Gy total body irradiation at 4 d after drug injection and then once a day for 5 days.The tumor inhibition efficiency,the number of bone marrow cells,thymus indices,and spleen indices were evaluated.Results Tumor weights in each drug group were significantly lower than those of the control( t =4.58,9.07,6.67,P ＜ 0.05 ).Drug combinated with 137Csγ-rays enhanced the antitumor effect so that the tumor weights in the combination group were significantly decreased ( t =8.06,10.35,6.71,P ＜0.05 ) in comparison with the control groups.Moreover,the numbers of marrow nucleated cells,thymus index and spleen index in the drug group were higher than those in the control group ( t =2.64,3.80,2.84,P ＜ 0.05 ).Conclusions 17aα-D-homo-ethynylestrudiol-3-acetae can inhibit cell growth of B16 melanoma in mice and may also have radioprotective effect on the hematopoietic system and immune system of mice.

Research advances in cell surface ATP synthase / 上海第二医科大学学报

Mitochondria ATP synthase is a key enzyme in cellular energy interconversion. It is generally believed that ATP synthase is strictly confined to mitochondria. However, it has been demonstrated that ATP synthase also occurs on the extracellular surface of vascular endothelial cells, tumor cells and adipocytes, instead of normal cells. Based on this characteristic, many functional researches have been conducted on the angiogenesis, tumor inhibition and lipid metabolism, and the mechanism on which this enzyme works has been preliminarily elucidated. The research advances in cell-surface ATP synthase are reviewed in this paper.