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Objective: To investigate the effect of low-dose paclitaxel combined with thalidomide on angiogenesis in mice bearing S180 sarcoma. Methods: An S180 sarcoma-bearing mouse model was established. Forty tumor-bearing mice were randomly divided into four groups: A, the control group, administered normal saline; B, the paclitaxel group, administered 20 mg/kg paclitaxel by intraperitoneal injection three times per week for 2 weeks; C, the thalidomide group, administered 200 mg/kg thalidomide by gavage three times per week for 2 weeks; and D, the paclitaxel + thalidomide group, administered paclitaxel (20 mg/kg) and thalidomide (200 mg/kg) by intraperitoneal/intragastric administration three times per week for 2 weeks. Tumor weight, tumor inhibition rate, microvascular density (MVD), and vascular endothelial growth factor (VEGF) expression were measured. Results: Tumor weight, VEGF expression, and MVD were lower in groups B, C, and D (P<0.05) than in the control. VEGF expression and MVD were lower in group D than in groups B and C; these differences were statistically significant (P<0.05). Conclusions: Low-dose paclitaxel combined with thalidomide exerted an inhibitory effect on vascular growth in S180 sarcoma.
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Objective: To investigate the anti-tumor activity in vivo of sesquiterpenoids from ginseng (SPG) in the S180 tumor-bearing mice, and to clarify its mechanism Methods: The ICR male mice were used to establish the S180 tumor-bearing models. The model mice were randomly divided into model group, 5-fluorouracil (5-FU) group (20 mg • k g- 1 , ip), low dose of SPG group (2. 5 mg • k g- 1 , ig), and high dose of SPG group (10. 0 mg • k g- 1 , ig), 8 mice in each group; another 8 mice were selected and used as blank control group. Fourteen days after administration, the blood samples were collected from the eyes of all mice, and they were sacrificed by cervical dislocation, then the tumor tissue was excised and weighed; the inhibitory rate of tumor was calculated; the serum levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), urea nitrogen (BUN), interleukin-2 (IL-2), tumor necrosis factor-a (TNF-a) and vascular endothelial growth factor (VEGF) of the mice in various groups were measured; the pathological changes of the tumor tissue of the mice in various groups were observed by HE staining; the expression levels of anti-apoptotic factor Bel-2, VEGF, p38 against mitogen-activated protein kinase (p38MAPK) and p-p38 against mitogen-activated protein kinase (p-p38MAPK) in the tumor tissue of the mice in various groups were analyzed by Western blotting method. Results: The inhibitory rates of the mice in SPG groups were increased significantly as the increase of SPG dose, and the inhibitory rate of tumor of the mice in high dose of SPG group was 76. 29%. Compared with model group, the serum levels of IL-2 and TNF-a of the mice in SPG groups were significantly increased (P < 0 . 01) and the levels of ALT, AST, BUN and VEGF were significantly decreased (P < 0. 05 or P< 0. 01). The HE staining results showed that the cells in model group were arranged neatly, a large number of nuclei were observed and the growth state was good; in low and high doses of SPG group, the number of nuclei in the tumor tissue of the mice was significantly reduced, the arrangement was loose, and a large area of necrosis occurred. The Western blotting results showed that compared with model group, the expression levels of Bcl-2 and VEGF proteins were significantly decreased (P < 0 . 01) and the expression levels of p-p38MAPK protein in low and high doses of SPG groups were significantly increased (P < 0.01). Conclusion: SPG has a good anti-tumor effect in the S180 tumor-bearing mice, and its mechanism may be associated with the decreasing of Bcl-2 and VEGF expressions and activation of p38 MAPK protein channel.
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This study examined the effect of saponins from Tupistra chinensis Bak (STCB) on the growth of sarcoma S-180 cells in vitro and in mouse xenografts as well as the underlying mechanisms.Cell proliferation was assessed by MTT assay.Cell cycle distribution was determined by flow cytometry.Sarcoma S-180 tumor-bearing mice were treated with different doses of STCB with 10 μg/mL 5-fluorouracil (5-Fu) as a positive control.The activity of nuclear factor (NF)-κB was detected by gel mobility shift assay.The mRNA level of NF-κB was determined by real-time quantitative RT-PCR.The results showed that in vitro STCB inhibited the growth of S-18 0 cells in a concentration-dependent manner,which was accompanied by cell cycle arrest at S-phase.In vivo STCB significantly inhibited the growth of S-180 tumor mouse xenografts in a dose-dependent manner with apparent induction of cell apoptosis.Moreover,STCB inhibited the activity of NF-κB p65 and reduced the expression of NF-κB p65 mRNA in mouse xenografts.It was concluded that STCB inhibits the proliferation and cell cycle progression of S-180 cells by suppressing NF-κB signaling in mouse xenografts.Our findings suggest STCB is a promising agent for the treatment of sarcoma.
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This study examined the effect of saponins from Tupistra chinensis Bak (STCB) on the growth of sarcoma S-180 cells in vitro and in mouse xenografts as well as the underlying mechanisms.Cell proliferation was assessed by MTT assay.Cell cycle distribution was determined by flow cytometry.Sarcoma S-180 tumor-bearing mice were treated with different doses of STCB with 10 μg/mL 5-fluorouracil (5-Fu) as a positive control.The activity of nuclear factor (NF)-κB was detected by gel mobility shift assay.The mRNA level of NF-κB was determined by real-time quantitative RT-PCR.The results showed that in vitro STCB inhibited the growth of S-18 0 cells in a concentration-dependent manner,which was accompanied by cell cycle arrest at S-phase.In vivo STCB significantly inhibited the growth of S-180 tumor mouse xenografts in a dose-dependent manner with apparent induction of cell apoptosis.Moreover,STCB inhibited the activity of NF-κB p65 and reduced the expression of NF-κB p65 mRNA in mouse xenografts.It was concluded that STCB inhibits the proliferation and cell cycle progression of S-180 cells by suppressing NF-κB signaling in mouse xenografts.Our findings suggest STCB is a promising agent for the treatment of sarcoma.
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OBJECTIVE:To study the antitumor effect of phellinus linteus polysaccharide on sarcoma S180 cells in vivo and in vitro. METHODS:Sarcoma S180 cells in logarithmic growth period were selected,adding into 0(blank control),2,4,8 mg/mL phellinus linteus polysaccharide solution and respectively culturing for 12,24,36,48 h. The in vitro proliferation inhibition rate of cells was determined by MTT method;its apoptotic morphology was observed by fluorescence staining and cell apoptosis rate was detected by flow cytometry. S180 tumor-bearing mice models were established and randomly divided into control group,phellinus linteus polysaccharide high-dose,medium-dose,low-dose groups(400,200,100 mg/kg),10 in each group. Model mice were in-tragastrically administrated related medicined,once a day,for 12 d. Mice were executed after 24 h of last administration,tumor weight was determined,tumor inhibition rate was calculated. Immunohistochemistry was conducted to detect the tumor suppressor gene PTEN and oncogene C-myc protein expressions in tumor tissue. RESULTS:Compared with blank control group,phellinus linteus polysaccharide can increase the proliferation inhibition rate of S180 cells and induce the increase of apoptosis rate(P<0.05 or P<0.01),showing a concentration-time manner. Compared with control group,the tumor inhibition rates in phellinus linteus polysaccharide groups were obviously increased (P<0.01),PTEN protein expressions were strengthened (P<0.05 or P<0.01) and C-myc protein expressions were weakened (P<0.05). CONCLUSIONS:Phellinus linteus polysaccharide shows antitumor ef-fect in vivo and in vitro,which can up-regulate the PTEN,down-regulate C-myc protein expressions.
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Objective To study the antitumor activity of Xerophilusin G on S180 cells,and Its mechanism.Methods Modified MTT assay was used to test the effect of Xerophilusin G on the proliferation of S180 tumor cell strain.The influences on tumor growth and immune organs of mice with transplanted sarcoma (S180) were observed.The cell cycle of S180 cell lines and mouse sarcoma (S180) was analyzed by flow cytometry.The lymphocyte proliferation activity of spleen stimulating was tested.The level of IL-2 in serum of mice with transplanted sarcoma (S180) was measured by ELISA.Results The IC50 of Xerophilusin G in S180 cell lines was 19.80 μg·mL-1,the LD50 in mouse for Xerophilusin G was 121.11 mg·kg-1 through intraperitoneal injection.The tumor inhibition rate of Xerophilusin G was 32.11% and 41.60%,respectively at the doses of 3 and 6 mg · kg-1 (P < 0.05).Compared with the control,the thymus,kidney and cardiac index were decreased.The cell proportion at G0/G1 phase of mouse sarcoma (S180) was increased.T and B cell proliferation activities in tumor-bearing mice were enhanced (P < 0.05).As compared with control group,the serum level of IL-2 was decreased 90.9% and 77.1% in low-and medium-dose groups,respectively (P < 0.05).Conclusion Xerophilusin G has remarkable effects in sarcoma (S180) bearing mice.The antitumor mechanism of Xerophilusin G might be related with G0/G1 phase arrest of mouse sarcoma (S180) cells and enhancing the activity of T and B cell but not related with increasing the secreting of IL-2.
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OBJECTIVE:To study the anti-tumor effects of Vinblastine (VLB) hydrophilic group modified cationic liposomes in tumor-bearing mice. METHODS:Tumor-bearing model were induced by inoculating yellow ascites of S180 ascites tumor mice. Tumor-bearing mice were randomly divided into model group,VLB sulfate injection group,VLB liposomes group,VLB hydrophil-ic group modified liposomes group,VLB cationic liposomes group and VLB hydrophilic group modified cationic liposomes group, i.e. group A,B,C,D,E and F,with 18 mice in each group. Group A was given normal saline intravenously via mice tail,other groups were given VLB 1.5 mg/kg every 2 days for consecutive 5 times. The anti-tumor effects of different VLB preparations were compared,using living conditions,survival time,tumor volume and weight,and tissue pathological section as indexes. RE-SULTS:Compared with group A,B,C,D and E,the mice of group F were more active,and had longer survival time,smaller tumor volume and lighter tumor weight,with statistical significance(P<0.05). The tissue pathological section of mice in group F indicated that coagulation necrosis,disintegration,and dissolution of tumor cell nucleus. CONCLUSIONS:VLB hydrophilic group modified cationic liposomes have obvious anti-tumor effect,which are better than other VLB preparations.
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Objective: To explore the inhibitory mechanism of polypeptide extract from scorpion venom (PESV) on sarcoma S180. Methods: Thirty mice were implanted with S180 cells and randomly divided into three groups: control group, PESV group, and rapamycin (RAPA) group with 10 mice in each group. Then the tumor volume growth curve was drawn and the tumor inhibitory rate (IR) was calculated. The morphological changes of the tumor tissue were observed by HE staining. The protein expression levels of Beclin1, MAP1LC3A, and CD133 were detected using immunohistochemical assay. Western blotting was applied to detecting the expression of Beclin1, MAP1LC3A, and CD133 in tumor tissue of mice in each group. Results: The growth of sarcoma S180 transplanted tumor was inhibited more obviously in the PESV group and RAPA group than that in the control group. The IR in the PESV and RAPA groups were 17.9% and 25.0%, respectively (P 180, the mechanisms might be associated with promoting the expression of autophagic relative factors, Beclin1 and MAP1LC3A as well as inhibiting the expression of CD133.
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Objective: To study the effect of Qinglongyi polysaccharides (QP) in the exocarp of Juglans mandshurica on the complex mobility of erythrocytes in S180 mice. Methods: Erythrocytes were collected and prepared into suspensions, and the complex mobility of cells was measured using high performance capillary electrophoresis (HPCE). Optimized experimental conditions were as follows: 50 cm × 75 μm capillary, buffer for electrophoresis; phosphate solution containing hydroxypropylmethyl cellulose (0.1 mol/L, pH 7.4), injection pressure 3.448 kPa, injection time 10 s, separation voltage 20 kV, and column temperature 25 °C. Results: The migration time of erythrocytes in S180 mice was longer than that in normal mice, which was 18.09 min for the model group and 12.11 min for the control group, and the complex mobility of erythrocytes in S180 mice was lower than that in normal mice, which was 0.92 × 10-4 cm2/(Vs) for the model group and 1.38 × 10-4 cm2/(Vs) for the control group. It was also found that S180 mice treated by QP could shorten the migration time and increase the complex mobility of erythrocytes. Conclusion: QP could improve the complex mobility of erythrocytes in S180 mice, and HPCE could be used as a powerful tool for determining the physiological state and functions of erythrocytes. © 2013 Tianjin Press of Chinese Herbal Medicines.
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This article was aimed to study the inhibitory effect of ginseng polysaccharide injection on tumor growth a-mong ICR mice after inoculation of S180 cells, and its immune mechanism as well as its synergic effect in reducing toxicity of cytoxan (CTX). The experiment was carried out in ICR mice after inoculation of S180 cells. The mice were randomly divided into the model group, the control group, the CTX group, and the drug combination group. After 10 days of medication, the inhibition of tumor growth, WBC, thymus index and spleen index were measured in mice dur-ing the experiment. The immunodepressed mice model was induced by CTX. Effects of ginseng polysaccharide injec-tion on serum hemolysin and monomuclear macrophage phagocytosis were evaluated. The results showed that the com-bination of ginseng polysaccharide injection and CTX can significantly increase the tumor inhibiting rate. It can also reduce the side effect and toxicity of CTX, which may improve the immunosuppression induced by CTX. It was con-cluded that ginseng polysaccharide injection can increase the therapeutic effects and reduce the toxicity of CTX.
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Objective Study the anti-tumor effects in vivo of AMH-D on S-180 cell lines, the synergistic effects of AMH-D and cyclophosphamide,and investigate the way and its strength of the effect. Provide the basis for the development of anti-cancer drug. Methods Kunming mice were transplanted with S-180 tumor cells subcutaneously in the right armpit. Intraperitoneal injection was done after randomization on the next day. Mice were killed on the eleventh day, and tumors were stripped and weighed. The tumor weight was used as indicator for analysis and evaluation. Results The results showed that AMH-D could effectively inhibit the growth of S180 cells transplanted tumor. The tumor inhibition rate was 50.45%at the dose of 150 mg/kg, with a dose-effect relationship. There were no obvious impacts on the growth of the weight of mice. The results showed that AMH-D had a synergistic effect combined with cyclophosphamide within a certain dose. Conclusion Fungus extract AMH-D has a great effect on anti-tumor in vivo of S180 cells transplanted tumor, and has a synergistic effect combined with cyclophosphamide within a certain dose.
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ObjectiveTo explore the antitumor effect of solanine and its mechanisms.MethodsThe in vivo antitumor effect of solanine was observed using models developed through in vivo transplantation of tumor cells; In vitro lines of sensitive antitumor cells were selected from the digestive system using MTT assay; The effect of solanine on cell morphology was observed using transmission electronic microscopy; The morphology of apoptotic cells was observed using Annexin V/PI double staining and laser confocal scanning microscopy (LCSM); The rate of cell apoptosis was measured using Annexin V/PI double staining and flow cytometry; The concentration of intracellular Ca2+ ([Ca2+]1) was determined using Fluo-3/AM staining and LCSM; The membrane potential of cellular mitochondria was determined using TMRE staining and LCSM; The protein expression of Bcl-2 and Bax was measured using immunological marking and LCSM; And the activity of caspase-3 was measured using the colorimetric method.ResultsSolanine could inhibit the growth of tumor weight in S180 tumor-bearing mice and prolong the survival time of H22 tumor-bearing mice.MTT assay revealed that HepG2 cells were quite sensitive to solanine because solanine could induce morphological changes in HepG2 cells,with the rate of early apoptosis being 4%,8.5%,and 20.1%,for HepG2 cells treated for 24 h with solanine at concentration of 0.4,2,and 10 μg/mL,respectively.Solanine could raise the [Ca2+]i and lower the membrane potential.It could reduce the protein expression of Bcl-2 while increase that of Bax,thus increasing the activity of caspase-3.ConclusionThe obvious antitumor activity of sotanine in human hepatocarcinoma is demonstrated.This inhibitory effect is achieved through solanine decreasing the Bcl-2/Bax ratio,thus increasing [Ca2+]i,which could enhance the enzymatic activity of the caspase family,thus inducing the apoptosis of HepG2 cells.
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Background and purpose: Mouse osteosarcoma model was widely used in osteogenic malignant tumor research, and it was helpful for studying the invasion and metastasis of the tumor cells when it was well marked in vivo. The purpose of this study was to establish mouse sarcoma cell lines (S180) that were infected with enhanced green fluorescent protein(EGFP). Methods: EGFP-S180 expressing strong EGFP fluorescence was acquired by electroblot, and supplemented with G418 (800 mg/mL), c-Myc was detected by laser scanning confocal microscopy. Meanwhile, the cancer-bearing model was established subcutaneously within the abdominal cavity. Results: EGFP-S 180 cells were cloned. There was no significantly difference between c-Myc expressions in S180 cells and those in EGFP-S180 cells (P>0.05), and between the cancer-bearing time subcutaneously and the time within abdominal cavity (P>0.05). Conclusion: According to in vitro and in vivo assay, it showed that EGFP-expressing S180 cells could be used for studying further the tumor biological behavior with fluorescence technology.
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Objective To study Baizhu's inhibitory effect on S180 sarcoma growth and its effect on Bcl-2 expression in tumor-transfected mice. Methods S180 cells were subcutaneously injected into 60 healthy Kunming mice. Meanwhile the mice were dealt with MTX or Baizhu, separately; the weight of tumor was measured in the following two weeks; the expression of Bcl-2 was detected by RT-PCR. Results The tumor's weight in Baizhu group was lower than that in model group, but higher than in MTX group (P<0.05), but Baizhu's inhibition was not associated with its dose (P>0.05), and Baizhu's rate of tumor growth inhibition was lower than that of MTX. Compared with that in control group, Bcl-2 expression was lower in Baizhu group obviously. Conclusion Baizhu can inhibit tumor growth and serve as an adjuvant drug in tumor therapy.
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Objective: To observe the anti-tumor effect of Phellinus Linteus and Coriolus Versicolor Capsules (PLCVC) in S180 sarcoma and H22 hepatoma animal models in mice. Methods: The sarcoma S1180 and hepatoma H22 models were established in mice. After 12 days of treatment, the animals were killed, and the subcutaneous sarcoma were separated and weighted. The levels of vascular endothelial growth factor(VEGF), CD4 and CD8 of S180 tumor tissue were investigated by immunohistochemical method. KM mice were intraperitoneal injected with H22 hepatoma cells, and treated with different experimental drugs. The survival time was observed and recorded, and life-prolongation rate was calculated. Result: PLCVC could inhibit the growth of S180 and H22 tumor, and inhibit the expression of VEGF, improve the expression of CD4 and CD8. The survival time of the mice treated by PLCVC were significantly longer than the untreated group. Conclusion: PLCVC can inhibit the growth of tumour, the mechanism is partially related to inhibiting angiogenesis and improving the immunological function.
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Objective To study the anti-tumor effect of water extracts from Sophora Moorcroftiana seed(SMSWE) in vivo on mice.Methods S180-bearing mice group were observed.The inhibitory rate of tumor,survival period,indexes of thymus and spleen,the proliferative ability of T lymphocytes were assayed.Results 1.2 and 2.4 g/kg SMSWE could inhibit the growth of S180 tumor in mice and prolonged survival period(P
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OBJECTIVE:To study the immunoregularoty effect of Lappaconitine in S180 tumor-bearing mice.METHODS: Each mouse was inoculated hypodermically with S180 tumor cells and normal sodium suspension,24 hours later,all the mice were injected i.m.with Lappaconitine q.d for 10 consecutive days.The immune function of the S180 tumor-bearing mice was detected.RESULTS: In Lappaconitine-treated mice,serum IgG level was heightened significantly;the 2,4-DNFB-induced delayed type hypersensitivity was enhanced;the induction of transformation of lymphocytes into lymphoblast was achieved;the phagocytic function of reticuloendothelial system was enhanced significantly,and the immune function of red cells was promoted.CONCLUSION: Lappaconitine could inhibit the growth of S180 tumor cells and significantly enhance the cellular immune function of S180 tumor-bearing mice.
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Objective To study the cell killing effect on isolated sarcoma 180 cells by ultrasound activating Protoporphyrin IX and to explore its biological mechanism.Methods The sonodynamical effect was investigated on S180 tumor cells exposed to the combination of 120 mol/L protoporphyrin Ⅸ (PPⅨ) and focused ultrasound at the frequency of 2.2 MHz and an intensity of 3W/cm2. The livability of cells was evaluated by trypan blue staining. Scanning electron microscope (SEM) observation of the surface of cells was performed to evaluate the morphological changes induced by ultrasonic irradiation. The generation of oxygen free radicals in cell suspensions was immediately detected after treatment by the active oxygen detection kit. Oxidative stress was assessed by measuring the activities of key antioxidant enzymes (ie, Superoxide dismutase[SOD], Glutathione peroxidase [GSH-PX], Catalase [CAT]) in S180 cells after SDT.Results The cell damage rate of ultrasound combined with PPIX was significantly higher than that treated with ultrasound alone only, and PPIX alone had no killing effect on S180 cells. Enzymatic chemical methods showed the content of MDA significantly increased after treatment, while the activities of key antioxidant enzymes in tumor cells all decreased at different levels, and was associated to the generation of oxygen free radicals in cell suspension after treatment. Conclusion Oxygen free radical may play an important role inimproving the membrane lipid peroxidation, decreasing the activities of key antioxidant enzymes in cells, and the biological mechanism might be involved in mediating the killing effect of S180 cells in SDT.
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Objective To study the inhibitory effects of total flavonoids of scutellaria baicalensis georgi(TFSB) on S180,Hep-A-22 and Bcap-37 tumor cell proliferation in vitro and on S180,Hep-A-22 in mice bearing tumor in vivo.Methods In vitro,S180,Hep-A-22 and Bcap-37 cells were divided into control group and TFSB groups(12.5,25.0,50.0,100.0 mg?L-1).The inhibitory effects of TFSB on proliferation of S180 and Hep-A-22 were measured by XTT colorimetric assay,and Bcap-37 cells were measured by MTT colorimetric assay.In vivo,the mice bearing tumor were divided into control group,CTX group(30 mg?kg-1),high,middle,low doses TFSB groups(200,100,50 mg?kg-1).After the mice bearing S180 and Hep-A-22 tumor cells were treated with TFSB for 15 d,the tumor weights were measured,the inhibitory rates of S180 and Hep-A-22 were calculated and survival of Hep-A22 was measured after administration of TFSB for 10 d.Results TFSB inhibited the proliferation of S180,Hep-A-22 and Bcap-37 cells,IC50 values were 16.04,17.74 and 9.05 mg?L-1,respectively.The tumor weight of mice bearing S180 and Hep-A-22 cells in TFSB groups(200,100,50mg?kg-1) were lowered than that in control(P
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Objective To discuss the tumor suppressing effect of cadmium chloride on S180 sarcoma,and to explore its favoriable dosage.Methods The mouse models bearing S180 sarcoma were treated with cadmium chloride with dosages of 0.25,1.00 and 4.00 mg?kg-1,the anti-tumor effect was evaluated by calculating of tumor weight;spleen and thymus indexes,carbon phage assay,lymphocyte transformed assay and hematolysis assay were used to measure the effect of cadmium chloride on immune function.Results Cadmium chloride with varied dosage of 0.25,1.00 and 4.00 mg?kg-1 inhibited the growth of S180 sarcoma,the tumor weights in cadmium chloride groups were significantly lower than that in control(P