| Objective: This study was conducted to investigate the effects of matrine on apoptosis of S180 sarcoma cells and the expression of death receptor pathway related proteins Caspase-8,Fas and Fas L.Methods: A mouse model of S180 sarcoma was established,30 mice were divided into 5 groups with 6 mice in each group.The mice were divided into control group with 10mg/kg matrine,25mg/kg matrine,50mg/kg matrine and 5mg/kg cisplatin.The control group was intragastric with normal saline,the matrine group was intragastric with different concentrations of matrine,the cisplatin group was intraperitoneally injected with cisplatin for 3 days.After 12 days of intragastric administration,the tumor body was taken out for study,and the weight of the tumor body was measured.The tumor inhibition rate and apoptosis of mouse sarcomas treated with normal saline and different concentrations of matrine were detected and compared by TUNEL method,immunohistochemical detection method,Western blot method,etc.Meanwhile,Caspase-8 activity and Fas/Fas L protein expression levels in S180 sarcoma tissues of mice were compared and analyzed.Results:1.The mean tumor weight of sarcomas in control group,matrine 10,25,50mg/kg group and cisplatin 5mg/kg group were(4.6±1.7)g,(3.1±1.2)g,(1.9±0.8)g,(1.5±0.6)g and(2.8±1.6)g.Compared with the control group,the tumor weight and tumor inhibition rate of the three matrine groups were significantly different(P<0.01).The tumor weight and tumor inhibition rate in matrine 25 and 50mg/kg groups were significantly lower than those in cisplatin group,and the difference was statistically significant(P<0.01).2.The number of apoptotic cells in the control group was rare,and the apoptotic rate was(2.7±0.8)%.The apoptotic cells in matrine 10,25 and 50mg/kg groups were significantly increased(32.8±4.9)%,(39.6±7.2)% and(46.7±9.4)%,respectively,which had significant statistical difference compared with the normal control group(P<0.01),and showed a positive correlation with the concentration of matrine.The apoptosis rate of the cisplatin group was(37.8±8.4)%,and the apoptosis rate of the matrine 25 and 50mg/kg groups was higher than that of the cisplatin group,with statistically significant difference(P<0.01).3.Caspase-8 activity increased gradually,and the differences were statistically significant(P<0.01).Caspase-8 activity increased with the increase of matrine concentration,showing a significant concentration dependence.Caspase-8 activity in matrine 25 and 50mg/kg groups was higher than that in cisplatin group,and the difference was statistically significant(P<0.01).4.Immunohistochemical observation showed that Fas staining and Fas L staining in sarcoma tissues were brownish yellow,Fas staining and Fas L staining in the control group were relatively light,while Fas staining and Fas L staining in the low,medium and high concentration matrine groups were significantly increased compared with the control group,with statistical significance(P<0.05).The increase was most significant in the high concentration matrine group.5.Western blot results showed that the expressions of Fas,Fas L and Caspase-8 in low,medium and high concentrations of matrine were significantly increased compared with the control group,with statistically significant differences(P<0.05),and the expressions of Fas,Fas L and Caspase-8 showed a positive correlation with the concentration of matrine.Conclusion:1.With the increase of matrine concentration,the tumor inhibition rate and apoptosis rate increased continuously,Caspase-8 activity increased gradually,and Fas and Fas L staining also deepened gradually,showing a significant concentration dependence.2.Matrine regulates the apoptosis of tumor cells through Fas/Fas L signaling pathway. |
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