胃癌细胞对化疗药物的敏感性及其与Pgp、GST-π和Topo Ⅱ表达的关系

RELASHIONSHIP BETWEEN EXPRESSIONS OF Pgp,GST-π,ToPo Ⅱ AND SENSITIVITY TO CHEMOTHERAPEUTIC DRUGS IN GASTRIC CARCINOMA

目的探讨胃癌在体外对化疗药物的敏感性和与P-糖蛋白(P-glycoprotein Pgp)、谷胱甘肽S转移酶π(glutathione-S-transferase GST-π)和拓扑异构酶Ⅱ(topoisomeraseⅡ TopoⅡ)表达的关系。方法收集81例手术切除胃癌标本,制备单细胞悬液,分别加入HCPT、CDDP、ADM、5-Fu和MMC培养48h,用MTT比色法检测胃癌细胞对化疗药物的敏感性;免疫组化技术检测Pgp、GST-π和TopoⅡ蛋白在胃癌组织中的表达。结果胃癌细胞对不同化疗药物敏感性不同:5-Fu(43.4±9.2)、CDDP(41.9±8.7)和HCPT(40.6±8.3)对胃癌细胞的抑制率与ADM(31.6±7.8)和MMC(28.7±7.3)比较有统计学意义(P<0.05)。胃癌组织中Pgp、GST-π和TopoⅡ蛋白的阳性率分别为61.33%、65.33%和68.00%。Pgp阳性者显示对ADM、HCPT有明显的体外耐药性(P<0.05),GST-π在5-Fu、CDDP和MMC耐药组阳性率显著高于敏感组(P<0.05),而TopoⅡ在HCPT、ADM和MMC耐药组中的表达显著低于敏感组(P<0.05)。结论 Pgp、GST-π和TopoⅡ可以作为胃癌对化疗药物原发性耐药的标志,结合MTT药敏检测,有助于筛选有效化疗药物。

Objective To investgate in vitro the relationship between expressions of Pgp, GST-π,TopⅡ and sensitivity to chemotherapeutic drugs in gastric carcinoma.Methods 81 samples of gastric cancer obtained from operating rooms were prepared to single-cell suspension and separately exposed to HCPT, CDDP, 5-Fu, ADM, MMC for 48 hours. The sensitivity of gastric cancer cells to chemotherapeutic drugs was evaluated with MTT assay,and expressions of Pgp,GST-π and TopⅡwas detected by immunohistochemistry.Results The sensitivity of gastric carcinoma cells to chemotherapeutic drugs was different. Inhibitory rates of tumor cell exposed to 5-Fu（43.4±9.2）,CDDP（41.9±8.7）and HCPT（40.6±8.3） were significantly higher than those of cells exposed to ADM（31.6±7.8） and MMC（28.7±7.3）（P0.05）.The positive rate of Pgp,GST-πand TopoⅡin gastric cancer was respectively 61.33%,65.33% and 68.00%.Pgp positive cells showed resistance to ADM and HCPT.GST-π expression was remarkably higher in the resistance than that in the sensitivity to 5-Fu,CDDP and MMC.TopoⅡ expression was significantly lower in the resistance to HCPT,ADM and MMC than that in the sensitivity group.Conclusion Pgp,GST-πand TopoⅡmay contribute to primary drug-resistance of tumor. Detection of Pgp,GST-π and Topo-Ⅱ,together with MTT chemosensitivity test, could constitute the prediction on applying chemo-drugs and identify drug-resisting cases.