Anticancer effects of disulfiram: a systematic review of in vitro, animal, and human studies.

BACKGROUND AND OBJECTIVES: Cancer morbidity and mortality rates remain high, and thus, at present, considerable efforts are focused on finding drugs with higher sensitivity against tumor cells and fewer side effects. Disulfiram (DSF), as an anti-alcoholic drug, kills the cancer cells by inducing apoptosis. Several preclinical and clinical studies have examined the potential of repurposing DSF as an anticancer treatment. This systematic review aimed to assess evidence regarding the antineoplastic activity of DSF in in vitro and in vivo models, as well as in humans. METHODS: Two authors independently conducted this systematic review of English and Chinese articles from the PubMed, Embase, and the Cochrane Library databases up to July 2019. Eligible in vitro studies needed to include assessments of the apoptosis rate by flow cytometry using annexin V/propidium iodide, and studies in animal models and clinical trials needed to examine tumor inhibition rates, and progression-free survival (PFS) and overall survival (OS), respectively. Data were analyzed using descriptive statistics. RESULTS: Overall, 35 studies, i.e., 21 performed in vitro, 11 based on animal models, and three clinical trials, were finally included. In vitro and animal studies indicated that DSF was associated with enhanced apoptosis and tumor inhibition rates, separately. Human studies showed that DSF prolongs PFS and OS. The greatest anti-tumor activity was observed when DSF was used as combination therapy or as a nanoparticle-encapsulated molecule. There was no noticeable body weight loss after DSF treatment, which indicated that there was no major toxicity of DSF. CONCLUSIONS: This systematic review provides evidence regarding the anti-tumor activity of DSF in vitro, in animals, and in humans and indicates the optimal forms of treatment to be evaluated in future research.

Low-activity 125I implantation into VX2 tumor rabbits and quantitative evaluation of the precise therapeutic effect.

There is still controversy about quantitatively evaluating the therapeutic effect of radioactive low-activity iodine-125 seeds (125I seeds). In the present study, a paired VX2 tumor model in a rabbit hind leg muscle was established, which is virus-induced anaplastic squamous cell carcinoma characterized by hypervascularity, rapid growth and easy propagation in the skeletal muscle. 125I seeds with 0.4 and 0.7 mCi activity were implanted into the left and right legs, respectively, using a radiation treatment planning system under positron emission tomography (PET)/computed tomography (CT) guidance. PET/CT scans and hematoxylin and eosin staining were observed at 72 h and 2 and 4 weeks after implantation to assess the therapeutic effect. The results showed that the average tumor length and standard uptake value (SUV) decreased over time, and both 125I seed groups achieved therapeutic effects at 4 weeks post-implantation. Quantitative evaluation of tumor inhibition rate, SUV variation and tumor marker ratio (Bcl-2/Bax) suggested that 0.7 mCi 125I seeds were more suitable than 0.4 mCi seeds in a clinical setting.

Injectable peptide hydrogel as intraperitoneal triptolide depot for the treatment of orthotopic hepatocellular carcinoma.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C16-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days in vitro, with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Ultrasound-guided intertumoral injection of contrast agents combined with human p53 gene for the treatment of breast cancer.

The objective of this study was to investigate the effects of ultrasound-guided injection of ultrasound contrast agents (UCAs) and the p53 gene on the treatment of rats with breast cancer (BC). Assembly of the p53 expression vector as well as that of a rat model with BC consisted of 200 successfully modeled rats randomly divided into 5 groups: p53 gene introduction, p53 gene introduction + ultrasound irradiation, p53 gene introduction + UCAs, p53 gene introduction + UCA + ultrasound irradiation, and UCA + ultrasound irradiation groups. Expression of p53 was detected via quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemical staining. In the p53 gene introduction + ultrasound irradiation group, we observed increased tumor volume with blood flow signals around and necrotic tumor tissues with an inhibition rate of 36.30%, as well as higher expression of p53 than that in the p53 gene introduction group and p53 gene introduction + UCA group. In the p53 gene introduction + UCA + ultrasound irradiation group, tumor volume increased slightly with reduced blood flow signals and massive degenerative necrosis of tumor cells was identified with inhibition rate of 62.62%, and expression of p53 was higher than that in the rest groups. Taken together, the key findings obtained from the present study elucidate that injection of p53 gene and UCA microbubbles guided by ultrasound could increase the expression of p53, thus inhibiting the tumor growth in rats with BC.

Inhibitory effect of aloe emodin mediated photodynamic therapy on human oral mucosa carcinoma in vitro and in vivo.

We report a study on inhibition of human oral squamous cell carcinoma in vitro and in vivo, using novel photosensitizer (PS) aloe emodin (AE) mediated photodynamic therapy (PDT). Distinct morphology changes of oral mucosa carcinoma KB cells were observed under an optical microscope and cell migrations were inhibited owing to AE-PDT. The cell proliferation was blocked in G1 phase and the apoptosis increase were both caused by massive reactive oxygen species (ROS) generated from photoactivated AE. The upregulation of Caspase-3 and Bax protein levels and downregulation of Bcl-2 protein levels were observed after AE-PDT. The survival time of tumor mouse was prolonged without side effects ascribed to AE-PDT and its inhibitory effect on mice transplantation tumors was significant. It is indicated that AE mediated PDT is an innovative way to oral cancer treatment with the dominances of effectivity, minimal invasion, tissue integrity retention and none side effects on main organs.

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.

Inhibition of the IGF signaling pathway reverses cisplatin resistance in ovarian cancer cells.

BACKGROUND: This study was aimed at investigating whether metformin can reverse the resistance of ovarian cancer cells to cisplatin and exploring the underlying mechanism. METHODS: Ovarian cancer cell proliferation in vitro was evaluated using a CCK-8 assay. The resistance index of platinum-resistant ovarian cancer cells was determined and cell cycle and apoptosis rate determined by annexin V/propidium iodide double-staining in CP70 cells. Western blotting was used to determine IGF1, IGF1R, AKT, p-IGF1, p-IGF1R, p-AKT, and MRP2 levels in cells treated with different concentrations of metformin and LY29400, an inhibitor of the insulin-like growth factor pathway. Changes in gene expression levels of MRP2, IGF1, IGF1R, and AKT were determined by fluorescence real-time quantitative PCR assay of CP70 cells treated with metformin. Tumors of human ovarian cancer cell lines CP70 and A2780 were established by subcutaneous transplantation of cells in nude mice and the effect of metformin on MRP2 expression and tumor inhibition assessed. RESULTS: The IC50 value of cisplatin in CP70 cells decreased significantly as metformin concentration increased (P < 0.05). The cell cycle distribution in CP70 cells changed with metformin treatment; the percentage of cells in the G0/G1 phase, as well as the natural apoptosis rate was significantly increased with metformin treatment (P < 0.05). IGF1, IGF1R, AKT p-IGF1, p-IGF1R, and p-Akt protein expression was enhanced dose-dependently with metformin, and was also significantly changed by treatment of CP70 cells with 0 mM metformin +10 mM LY294002. Moreover, changes in the expression of MRP2, IGF1, IGF1R, and AKT was metformin-concentration dependent, and was significantly different from that in the untreated control group (P < 0.05). In nude mice, the tumor volumes of the cisplatin-treated groups were significantly less than in the control group, and was further suppressed by co-treatment with cisplatin and metformin (P < 0.05), indicating that these 2 drugs had a synergistic effect on tumor inhibition. CONCLUSION: Metformin can improve the sensitivity of ovarian cancer CP70 cells to cisplatin in a concentration-dependent manner by activating the AKT signaling pathway, inhibiting the IGF1R signaling pathway, and reducing MRP2 expression.

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.

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.

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); B, the tumor inhibitory rate o f Group B had no statistical difference compared with Group 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.

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.

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.

Astragalus polysaccharides can regulate cytokine and P-glycoprotein expression in H22 tumor-bearing mice.

AIM: To investigate the adjunct anticancer effect of Astragalus polysaccharides in H22 tumor-bearing mice. METHODS: To establish a solid tumor model, 5.0 × 10(6)/mL H22 hepatoma cells were inoculated subcutaneously into the right armpit region of Kunming mice (6-12 wk old, 18-22 g). When the tumors reached a size of 100 mm(3), the animals were treated as indicated, and the mice were randomly assigned to seven groups (n = 10 each). After ten days of treatment, blood samples were collected from mouse eyes, and serum was harvested by centrifugation. Mice were sacrificed, and the whole body, tumor, spleen and thymus were weighed immediately. The rate of tumor inhibition and organ indexes were calculated. The expression levels of serum cytokines, P-glycoprotein (P-GP) and multidrug resistance (MDR) 1 mRNA in tumor tissues were detected using enzyme-linked immunosorbent assay, Western blotting, and quantitative myeloid-derived suppressor cells reverse transcription-polymerase chain reaction, respectively. RESULTS: The tumor inhibition rates in the treatment groups of Adriamycin (ADM) + Astragalus polysaccharides (APS) (50 mg/kg), ADM + APS (100 mg/kg), and ADM + APS (200 mg/kg) were significantly higher than in the ADM group (72.88% vs 60.36%, P = 0.013; 73.40% vs 60.36%, P = 0.010; 77.57% vs 60.36%, P = 0.001). The spleen indexes of the above groups were also significantly higher than in the ADM group (0.65 ± 0.22 vs 0.39 ± 0.17, P = 0.023; 0.62 ± 0.34 vs 0.39 ± 0.17, P = 0.022; 0.67 ± 0.20 vs 0.39 ± 0.17, P = 0.012), and the thymus indexes of the ADM + APS (100 mg/kg) and ADM + APS (200 mg/kg) groups were significantly higher than in the ADM group (0.20 ± 0.06 vs 0.13 ± 0.04, P = 0.029; 0.47 ± 0.12 vs 0.13 ± 0.04, P = 0.000). APS was found to exert a synergistic anti-tumor effect with ADM and to alleviate the decrease in the sizes of the spleen and thymus induced by AMD. The expression of interleukin-1α (IL-1α), IL-2, IL-6, and tumor necrosis factor-α (TNF-α) was significantly higher in the ADM + APS (50 mg/kg), ADM + APS (100 mg/kg) and ADM + APS (200 mg/kg) groups than in the ADM group; and IL-10 was significantly lower in the above groups than in the ADM group. APS could increase IL-1α, IL-2, IL-6, and TNF-α expression and decrease IL-10 levels. Compared with the ADM group, APS treatment at a dose of 50-200 mg/kg could down-regulate MDR1 mRNA expression in a dose-dependent manner (0.48 ± 0.13 vs 4.26 ± 1.51, P = 0.000; 0.36 ± 0.03 vs 4.26 ± 1.51, P = 0.000; 0.21 ± 0.04 vs 4.26 ± 1.51, P = 0.000). The expression level of P-GP was significantly lower in the ADM + APS (200 mg/kg) group than in the ADM group (137.35 ± 9.20 mg/kg vs 282.19 ± 20.54 mg/kg, P = 0.023). CONCLUSION: APS exerts a synergistic anti-tumor effect with ADM in H22 tumor-bearing mice. This may be related to its ability to enhance the expression of IL-1α, IL-2, IL-6, and TNF-α, decrease IL-10, and down-regulate MDR1 mRNA and P-GP expression levels.

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.

Study on the Antihepatocarcinoma Activity and the Acute Toxicity of Aclacimomycin-A Solid Lipids Nanoparticle for Injection in Mice in Vivo / 中国药房

OBJECTIVE:To study the antihepatocarcinoma activity and toxicity of Aclacimomycin-A solid lipids nanoparticle for injection(ACM-SLN)in nude mice in vivo with ACM for injection as the reference preparation.METHODS:The nude mice were divided into control group,ACM group and ACM-SLN group after tumor transplantation,which were injected with the corresponding medicine before the tumor-inhibition rates of which were calculated,which were then injected with ACM and ACM-SLN,respectively before the LD50 of mice were calculated.RESULTS:Compared with the control group,the tumor inhibition rates of ACM-SLN group and ACM group were 78.4%and 38.8%,respectively,the LD50 of which were 16.3 mg/kg and 18.0mg/kg,respectively.CONCLUSION:The ACM-SLN is superior to ACM in terms of the anti-tumor effect while without the increase of toxicity.

Antitumor activity and immunoregulatory effect of triterpenes isolated from betulaplatyphylla / 中国免疫学杂志

To study the antitumor activity and immunoregulatory effect of Triterpenes isolated from Betula Platyphylla (TBP)Methods: Inhihition rate (IR) on tumor growth was determined by the mice with transplantable tumors (melanoma B16, Sarcoma 180, Lewislung carcinoma and Ehrlich ascites cancer), splenocyte proliferation induced by ConA was measured by H-TdR incorporation; cytotoxicity ofmacrophage was observed by 3H-TdR release; activity of TNF and NK cell was determined by dye (natural red)release. Results: IR of 0.80 g/kg and 1.20 g/kg TBP on all of above tumor strains were greater than30％ in vivo. TBPdoes not show significant effect of splenocyte Prolifera-tion and NK cell activity, but significantly promoted the activity of TNF producted by macroghage and splenocyte. TBP also increase the cyto-toxicity of macrophage. Conclusion:TBP shows potent antitumor effect in vivo. Promoting nonspecific immunoactivity is one of the antitumormechanism of TBP.