Survivin Status Affects Prognosis and Chemosensitivity in Epithelial Ovarian Cancer
Survivin Status Affects Prognosis and Chemosensitivity in Epithelial Ovarian Cancer
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DOI：
10.1097/igc.0b013e31827ad2b8
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发表时间：
2013-02-01
影响因子：
4.8
通讯作者：
Zheng, Feiyun
中科院分区：
文献类型：
--
作者：
Chen, Lifeng;Liang, Lizhi;Zheng, Feiyun
目的：探讨Survivin在卵巢上皮性癌(EOC)中表达的临床意义及Survivin小发夹状RNA(ShRNA)对卵巢癌细胞株OVCAR3中Survivin表达、细胞凋亡及化疗敏感性的影响。免疫组织化学方法检测Survivin蛋白的表达。体外将Survivin shRNA导入OVCAR3细胞。逆转录-聚合酶链式反应检测Survivin基因表达水平。流式细胞仪检测Survivin蛋白表达水平和细胞凋亡率。结果：Survivin胞浆阳性表达与国际妇产科联合会(FIGO)分期、非粘液型、高级别及复发有关。Survivin阳性表达也与铂耐药有关(r=0.306，P=0.003)。统计学结果显示，FIGO分期(危险率=1.649，P=0.047)和Survivin胞浆表达(危险率=1.734，P=0.010)是影响预后的独立因素。转染Survivin重组载体的卵巢癌细胞(OVCAR3S)24小时后，Survivin的mRNA和蛋白水平均低于对照组。流式细胞仪分析显示Survivin shRNA诱导G0/G1期细胞积聚，培养24小时后G2/M期细胞减少(P<；0.01)。此外，Survivin shRNA使OVCAR3细胞对紫杉醇的敏感性增加15倍(P&t；0.05)，而对顺铂的敏感性无明显影响(P>；0.05)。结论：除FIGO分期外，胞浆Survivin蛋白的表达是预测卵巢癌预后的独立分子标志物。针对Survivin的序列特异性shRNA可以有效抑制Survivin的表达，促进细胞凋亡，增加卵巢癌细胞对紫杉醇的敏感性，但对顺铂的敏感性不高。
Objective: The objective of this study was to explore the clinical significance of survivin expression in epithelial ovarian cancer (EOC) and the effect of survivin small hairpin RNA (shRNA) on survivin expression, apoptosis, and chemosensitivity in the human ovarian cancer cell line OVCAR3.Methods: A retrospective review of 90 consecutive EOC patients with a median follow-up time of 51 months was conducted. Survivin expression was examined by immunohistochemistry. OVCAR3 cells were transfected in vitro with survivin shRNA. Survivin mRNA expression levels were detected using reverse transcription-polymerase chain reaction. Flow cytometry was applied to determine survivin protein expression levels and cell apoptotic rates. The MTT method was used to examine the effects of survivin shRNA on chemosensitivity in OVCAR3 cells.Results: Positive cytoplasmic expression of survivin was associated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, nonmucinous type, high grade, and recurrence. Positive survivin expression was also associated with platinum resistance (r = 0.306, P = 0.003). Statistical results indicated that FIGO stage (hazard rate = 1.649, P = 0.047) and cytoplasmic expression of survivin (hazard rate = 1.734, P = 0.010) were independent prognostic factors. Survivin mRNA and protein levels were lower in OVCAR3S (ovarian cancer cells transfected with a survivin recombinant vector) cells at 24 hours after transfection as compared with controls. The flow cytometric analysis revealed that survivin shRNA induced accumulation of cells in the G0/G1 phase, with a decrease in G2/M phase cells following 24 hours of culture as compared with a nontransfected group (P < 0.01). Furthermore, survivin shRNA increased the sensitivity of OVCAR3 cells to paclitaxel 15-fold (P < 0.05), whereas it had no significant effect on cisplatin (P > 0.05).Conclusions: In addition to FIGO stage, cytoplasmic survivin protein expression is an independent molecular marker for predicting EOC prognosis. Sequence-specific shRNA targeting survivin can effectively suppress survivin expression, enhance apoptosis, and increase the sensitivity of ovarian cancer cells to paclitaxel but not to cisplatin.