The Study Of Interaction And Mechanism Of Tiopronin Combined With Oxaliplatin On The Subcutaneously Transplanted Tumor Of Human Gastric Carcinoma In Nude Mice

Purpose:To study the interaction and mechanism of different concentration Tiopronin combined with invariably Oxaliplatin on the subcutaneously transplanted tumor of human gastric carcinoma in nude mice in vivo.Methods:1 The subcutaneously transplanted tumor models of human gastric carcinoma in nude mice were established and then were divided at random into 6 groups: A,B,C,D,E,F groups:;2 The weight detection of pre- and post-administration was carried out; The growth curve of transplantation tumor was drawed by measureing the diameter of tumor; The tumor inhibition rate was calculated by weigting the quality of tumor. The volume of tumor3 The blood routine examination and hepatic and nephritic functional examination were carried out to evaluate. and the pathological section of liver, kidney and tumor tissue were detected.4 The SOD of liver tissue was detected by colorimetric method;5 The Caspase-3 and ERCC-1 proteinum of transplantation tumor were detected by ElivisionTM-plus;6 The apoptosis rate of transplantation tumor was detected by TUNEL;7 The cell cycle was detected by FCMResults:1) The difference of the weight variation of athymic mouse was significant (P< 0.01) among groups; The weight of athymic mouse of B,D,E,F groups was descended. In contrast to pre- -administration, the difference was significant(P<0.01);2) The difference of the anti-tumor was significant (P<0.01) among groups; B,D,E,F groups Could obviously inhibit the growth of transplantable tumor with the tumor inhibitory rate of 31.60%,27.03%,23.48% and 20.56%,respectively;In contrast to the group of control, the difference was significant(P<0.01).No significant difference was found in tumor inhibition tates among E group in contrast to the group of F.3) The blood routine of B group was cut down, but D,E,F groups were seted up. The differencwere was significant (P<0.05) among groups. All groups no showed obviously hepatic and nephritic toxicity.4) With increasing of tiopronin, the activity of hepatic SOD was increasing; The difference of SOD was significant (P<0.05) among groups.The relation of SOD and AST,ALT was negative correlation5)The expression of Caspase-3 proteinum was situated in cytoplasm.The cytoplasm was buffy. L-OHP group compare with control group was X2=9.90 P=0.005; F group compare with L-OHP group was X2=7.50 P=0.02.The expression of ERCC1 proteinum was situated in nucleus mainly, meanwhile,it was situated in cytoplasm also. No significant difference was found in ERCC1 proteinum among groups.6)The apoptosis cells were situated in nucleus and were buffy drop.The difference of Apoptotic index was significant (P<0.01) among groups.7) With increasing of tiopronin dose,the percentage of S stage was larger; the percentage of G2/M stage was smaller.There were significant difference among groups in S stage and G2/M stage (p<0.01);Conclusion:1 Tio decrease the antitumor effect of L-OHP possiblly and decrease the hepatic toxicity of chemotherapeutics to cause.2 The growth of tumor and the doubleing time was shorten were caused possibly by SOD,which was created by tiopronin;The expression of ERCC1 in tumor tela was raised by tiopronin.It raised the drug fast of oxaliplatin possibly; The express ion of Caspas-3 in tumor tela was reduced by tiopronin.It reduced the apoptosis of tumor cell possibly.3 When were used tiopronin and oxaliplatin meanwhile,we must be careful in clini cal.