DNA聚合酶η蛋白表达差异与OVCR3细胞顺铂敏感性以及TP方案化疗的卵巢上皮癌患者临床疗效相关性分析

Correlative analysis on the relationship among the DNA polymerase expression variation and OVCR3 cell sensitivity to cisplatin and clinical efficacy in patients with epithelial ovarian cancer treated by Taxol and Cisplatin

目的:分析DNA聚合酶η蛋白的表达差异与OVCR3细胞顺铂敏感性以及TP方案(紫杉醇+顺铂)治疗的卵巢上皮癌患者临床疗效的关系。方法:体外培养OVCR3细胞,针对DNA聚合酶η蛋白编码基因的不同部位设计并合成3对靶向小分子RNA,通过脂质体介导瞬时转染OVCR3细胞,采用RT-PCR法比较细胞中DNA聚合酶η蛋白编码基因表达的差异,采用MTT法检测沉默DNA聚合酶η蛋白编码基因细胞对顺铂敏感性的变化。选取我院住院治疗的卵巢上皮癌患者50例,所有患者均为卵巢癌肿瘤细胞减灭术后采用TP方案(紫杉醇+顺铂)进行一线化疗。采用免疫组化法检测癌组织中的DNA聚合酶η蛋白表达,分析治疗效果与DNA聚合酶η蛋白表达之间的关系。结果:顺铂对OVCR3细胞株以及转染siRNA的OVCR3细胞株的IC50(半数抑制浓度)分别为(46.66±2.23)μmol/L、(30.21±3.09)μmol/L,差异有统计学意义(P<0.05)。目的蛋白表达差异与近期疗效有关,聚合酶表达强阳性组有效率为46.2%,阳性组有效率为60.0%,阴性组有效率为83.3%,三组比较差异有统计学意义(P<0.05)。DNA聚合η表达强阳性组中位生存时间为(15.7±3.6)个月,阳性组为(18.5±2.7)个月,阴性组为(28.3±1.9)个月,三组间比较差异有统计学意义(P<0.05)。结论:抑制DNA聚合η蛋白编码基因能够增加OVCR3细胞对顺铂的敏感性,且DNA聚合η蛋白表达量与TP方案化疗的近、远期疗效有相关性。

Objective： To explore the relationship among the DNA polymerase expression variation and OVCR3 cell sensitivity to Cisplatin and clinical efficacy in patients with epithelial ovarian cancer treated by Taxol and Cisplatin. Methods： OVCR3 cell were cultured and transfected by small interfering RNA with lipofectamine TM 2000. After transfection, expression of target gene was detected by RT-PCR. The cellular sensitivity to Csiplatin was evaluated by MTF assay. 50 patients with epithelial ovariana cancer were selected and treated by Taxol and Cisplatin. The expression of DNA polymerase η protein was evaluated by immunohistochemistry. The relationship between expression of DNA polymerase η protein and clinical efficacy were analysised. Results： The sensitivity to Cisplatin of OVCR3 cell and DNA polymerase η silencing were significantly different （P〈0.05） with half inhibitory concentration （46.66±2.23） μmol/L, （30.21±3.09） μmol/L respectively. The expression level of DNA polymerase η protein was correlative with the short-term clinical effect of Taxel and Cisplatin Chemotherapy. The response rates of strong positive expression group, positive group and negative group were 46.2%, 60.0%, 83.3% respectively. The differences were significant （P〈0.05）. The median survival times of three groups were （15.7±3.6） months, （18.5±2.7） months, （28.3±1.9） months. The differences were significant （P〈0.05）. Conclusion： The DNA polymerase η silencing could increase the cell sensitivity to Cisplatin. The expression of DNA polymerase η silencing is correlative to the clinical efficacy of Taxel and Cisplatin.