国际妇产科学杂志 ›› 2016, Vol. 43 ›› Issue (3): 335-339.

• 论著 • 上一篇    下一篇

Fn14活化凋亡增强人上皮性卵巢癌细胞顺铂敏感度的研究

吴安玥,邱丽华   

  1. 200127 上海交通大学医学院附属仁济医院妇产科,上海市妇科肿瘤重点实验室
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2016-06-22 发布日期:2016-06-22
  • 通讯作者: 邱丽华

Fn14 Enhances Cisplatin Sensitivity in Human Epithelial Ovarian Cancer Cells by Regulating Apoptosis

WU An-yue, QIU Li-hua   

  1. Department of Obstetrics and Gynecology, Shanghai Key Laboratory of Gynecology Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China
  • Received:1900-01-01 Revised:1900-01-01 Published:2016-06-22 Online:2016-06-22
  • Contact: QIU Li-hua

摘要: 目的:探讨成纤维细胞生长诱导因子14(Fn14)对人上皮性卵巢癌(epithelial ovarian cancer,EOC)细胞的顺铂(DDP)敏感度的影响及其可能机制。方法:蛋白质印迹(Western blotting)法检测EOC细胞株SKOV3、CAOV3、OVCAR3、ES2、3AO、A2780、A2780/DDP中Fn14蛋白的表达情况,选择低表达Fn14蛋白的细胞株转染Fn14过表达质粒后,观察转染后细胞株的Fn14蛋白、凋亡相关蛋白caspase-3、cleaved caspase-3和Bcl-2的表达情况。CCK-8法检测细胞增殖能力及DDP半数抑制浓度(IC50)。流式细胞学检测细胞凋亡。结果:人EOC细胞株SKOV3、CAOV3、OVCAR3、ES2、3AO、A2780、A2780/DDP中,A2780/DDP细胞株Fn14蛋白表达水平最低。Fn14过表达质粒转染A2780/DDP细胞后,细胞内Fn14表达水平上调(P<0.05);细胞的增殖能力无变化,但细胞DDP的IC50显著降低(P<0.05)。流式细胞学检测结果进一步显示Fn14可以增加DDP诱导的A2780/DDP凋亡细胞数目。同时,Western blotting结果显示促凋亡蛋白caspase-3表达升高,抗凋亡蛋白Bcl-2表达明显下降(P<0.05)。结论:Fn14可能活化凋亡通路进而提高A2780/DDP细胞对DDP的敏感度。

关键词: 卵巢肿瘤, 成纤维细胞生长诱导因子14, 顺铂, 抗药性,肿瘤, 细胞凋亡

Abstract: Objective: To investigate the effects of Fn14 on regulating cisplatin(DDP) sensitivity in human ovarian cancer cells. Methods: Fn14 protein expression levels in SKOV3, CAOV3, OVCAR3, ES2, 3AO, A2780 and A2780/DDP were detected through Western blotting. The expression of Fn14, caspase-3, cleaved caspase-3 and Bcl-2 were accessed by Western blotting in lowest expression of Fn14 cell line when transfected with Fn14 plasmid. The half cell lethal dose(IC50) of DDP and the ability of proliferation in A2780/DDP cells were assayed by CCK-8 kit. The ratio of apoptosis in A2780/DDP cells were determined by flow cytometry. Results: A2780/DDP cells exhibited the lowest expression of Fn14 in these cell lines. Fn14 transfer had no effect on the proliferation of A2780/DDP cells, whereas it could reduce the IC50 of DDP in A2780/DDP cells(P<0.05). When Fn14 was transferred, the apoptosis induced by DDP was increased in A2780/DDP cells, meanwhile, the expression of apoptosis-correlated protein caspase-3 was up-regulated and anti-apoptotic protein Bcl-2 was down-regulated(P<0.05). Conclusions: Fn14 may increase chemosensitivity to DDP by apoptosis pathway in human epithelial ovarian cancer cells.

Key words: Ovarian neoplasms, Fn14, Cisplatin, Drug resistance,neoplasm, Apoptosis