顺铂杀伤原代胃癌细胞效应与P-糖蛋白和谷胱甘肽S转移酶表达的关系  

ANTITUMOR EFFECT OF CISPLATIN IN VITRO ON FRESH HUMAN GASTRIC CANCER AND ITS RELATIONSHIP TO GLUTATHIONE S TRANSFERASE-π AND P-GLYCOPROTEIN EXPRESSION

作　　者：李树发[1] 尹浩然[1] 张俊[1] 燕敏[1] 朱正纲[1] 林言箴[1] 

机构地区：[1]上海第二医科大学附属瑞金医院外科,200025

出　　处：《中国现代医学杂志》2003年第12期23-25,共3页China Journal of Modern Medicine

基　　金：上海市医学发展基金资助 (编号 983 0 0 8)

摘　　要：目的 :评价顺铂 (CDDP)对原代胃癌细胞的体外杀伤效应 ,及其与胃癌组织P -糖蛋白和谷胱甘肽S转移酶表达的关系。方法 :采用纯化后的人新鲜胃癌细胞 ,用台盼蓝染色法和MTT法检测经顺铂作用后细胞活力及代谢活性的变化 ,用TdT法检测顺铂体外促凋亡效应 ;同时用SABC免疫组化法检测GST -π和P - gp表达 ,以研究其间的关系。结果 :经顺铂作用后 ,体外培养的胃癌细胞出现明显的形态学改变和代谢活性的下降 ;不同个体肿瘤细胞对顺铂敏感性不同 ,低分化胃癌细胞较高分化者更敏感 (4 1.2 5 %vs 33.2 3% )。经顺铂作用后 ,肿瘤细胞凋亡率增加 ,为 33.2 1%。 39例胃癌标本GST -π和P -gp的表达阳性率分别为 6 6 .6 7%和5 8.97% ,前者表达阳性者对CDDP显示了较强的体外耐药性 ,而后者高表达与CDDP体外耐药性无关。结论 :顺铂可能通过包括诱导凋亡在内的多种途径杀伤原代胃癌细胞 ,尤对低分化者显示了明显的肿瘤杀伤效应。GST -π高表达可能影响CDDP对胃癌细胞的杀伤效应。Objective:To evaluate the antitumor effect of cisplatin in vitro on fresh human gastric cancer cells, and its relationship with the expression of glutathione S transferase -π(GST-π) and P-glycoprotein(P-gp) in human gastric cancer tissue.Methods:Highly purified gastric cancer cells were obtained from 39 resected primary lesions for the MTT assay and trypan blue exclusive assay. The degree of apoptosis induced by cisplatin was determined by TdT assay simultaneously. The expression of GST-π and P-gp were detected by immunohistochemistry.Results: Remarked morphologic and metabolic changes, which varied from one patient to another, were found in gastric cancer cells after exposure to cisplatin. Poorly differentiated gastric cancers were more sensitive to cisplatin than well differentiated ones (41.25% vs 33.23% ). The average apoptic rate induced by CDDP was 33.21% in fresh human gastric cancer cells. The resistance to CDDP in vitro was closely related to the expression of GST-π .Conclusions:A complex mechanism could be used to explain the antitumor effect of CDDP, which might be a good candidate in chemotherapy for poorly differentiated gastric cancers. Detection of GST-π expression, together with chemosensitivity test, might be useful for predicting the chemosensitivities of the gastric cancer to cisplatin.

关 键 词：胃肿瘤 顺铂 谷胱甘肽S转移酶Π P糖蛋白 

分 类 号：R735.2[医药卫生—肿瘤]