TopoⅡα、GST-π、P-gp对卵巢癌患者化疗反应及预后预测的体内外实验  

Value of TopoⅡα,GST-π and P-gp in Predicting Chemotherapeutic Response and Prognosis of Ovarian Cancer in vivo and in vitro

作　　者：蔡鸿宁[1] 陈慧君[1] 吴绪峰[1] 龚玲玲[2] 曾俊[2] 

机构地区：[1]湖北省妇幼保健院妇瘤科,武汉430070 [2]武汉大学中南医院病理科

出　　处：《肿瘤防治研究》2012年第8期985-991,共7页Cancer Research on Prevention and Treatment

基　　金：湖北省科技厅自然基金一般项目(2010CDB10902);湖北省妇幼保健院院课题基金资助项目(20922004)

摘　　要：目的研究TopoⅡα、GST-π、P-gp在卵巢癌耐药中的作用及其对化疗反应及预后的预测价值。方法免疫组织化学SP法检测TopoⅡα、GST-π、MDR-1/P-gp在80例上皮性卵巢癌组织中的表达,分析它们与化疗反应及预后的关系;RNA干扰封闭GST-π、MDR-1/P-gp在人卵巢癌耐药细胞中的表达,检测其逆转细胞耐药的可能性。结果 TopoⅡα阴性和阳性患者的化疗反应无差异。GST-π阴性患者的化疗疗效显著优于阳性者(P=0.009);P-gp阴性患者也较阳性者疗效好,但差异无统计学意义(P=0.059)。尽管Log-rank test显示GST-π或P-gp阴性患者的生存时间显著长于相应指标阳性患者,但Cox分析并未指示两者为独立预后因素(P=0.682;P=0.101)。根据GST-π、P-gp的共同表达情况进一步分组分析显示,两者共同阴性的患者化疗有效率100%、85.7%生存至末次随访,GST-π、P-gp共同阴性预示较好的化疗反应及预后(P=0.012;P=0.000)。体外实验显示,卵巢癌耐药细胞对多种化疗药物敏感度降低,同时GST-π、MDR-1/P-gp mRNA表达增高。结论 GST-π及MDR-1/P-gp在卵巢癌耐药中具重要作用,GST-π或P-gp单独预测化疗反应及预后的效用有限,联合检测可提供较高临床价值,封闭两者表达可一定程度逆转卵巢癌细胞的耐药性。Objective To assess the role of TopoⅡα,GST-π and P-gp in drug-resistance of ovarian cancer and their value as predictors of chemotherapeutic response and prognosis.Methods The expression of GST-π,P-gp and TopoⅡα in the surgical specimens were detected by immunohistochemistry and their relationship with the chemotherapeutic response and prognosis of the patients were analyzed.The expression of GST-π and MDR-1/P-gp in human ovarian cancer cells was silenced by RNA：to evaluate the feasibility of reversal MDR phenotype in the cells.Results Chemotherapeutic response was no difference with negative TopoⅡα and positive.Chemotherapeutic response was more favorable in patients with negative GST-π than in those with positive expression（P=0.009）.Similar trend occurred with P-gp,though the difference was not significant（P=0.059）.Although log-rank test showed a longer survival in patients with negative GST-π or P-gp（P=0.012;P=0.000）,Cox hazard analysis did not indicate they could be regarded as prognostic predictors（P=0.682;P=0.101）.However,when their co-expression status was taken into account,it was found that 100.0% patients with co-negative GST-π/P-gp responded well to chemotherapy and 85.7% patients were still alive until the evaluation.Co-negative GST-π /P-gp presented better chemotherapeutic response and prognosis（P=0.001;P=0.000）.Furthermore,decreased drug sensitivity accompanied with overexpressed GST-π and P-gp level was found in MDR ovarian cancer cell lines.Conclusion GST-π and P-gp are involved in the forming of MDR in ovarian cancer.The reliability of MDR-1 and GST-π alone as indicators of chemotherapeutic response and prognosis is limited,and co-detection of their expression may provide a higher predictive value.After silencing the expression of GST-π and P-gp by RNAi,the drug sensitivity of the MDR cells were increased.

关 键 词：多药耐药 卵巢癌 谷胱甘肽-S-转移酶-Π P-糖蛋白 拓扑异构酶Ⅱα 

分 类 号：R737.31[医药卫生—肿瘤]