BNIP3 有助于顺铂诱导的卵巢癌细胞凋亡。,FEBS Open Bio

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BNIP3 有助于顺铂诱导的卵巢癌细胞凋亡。
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-06-27 , DOI: 10.1002/2211-5463.12881
Jinghui Jia _{1,

2} , Xiaoxin Yang ₃ , Qing Zhao _{2,

4} , Feiquan Ying ₂ , E Cai ₂ , Si Sun ₂ , Xiaoqi He ₂

Affiliation

BNIP3 是一种促凋亡蛋白，可介导细胞凋亡、坏死和自噬。然而，BNIP3 是否参与顺铂诱导的卵巢癌细胞凋亡尚不清楚。在这项研究中，我们检查了 BNIP3 在顺铂治疗期间卵巢癌中的作用及其与临床结果的相关性。我们首先测量了顺铂暴露前后卵巢癌细胞系 A2780、SKOV3、OVCAR4、OV2008、ES2 和 HO8910 的顺铂细胞毒性和 BNIP3 水平。观察到 BNIP3 在这些细胞系中差异表达，顺铂诱导 A2780 和 OVCAR4 中 BNIP3 水平显着增加。在 A2780 和 OVCAR4 中用 siRNA 敲低 BNIP3 显着降低了这两种细胞系中顺铂的细胞毒性，并减轻了顺铂诱导的细胞凋亡。我们搜索了在线数据库 Gene Expression Omnibus 和 The Cancer Genome Atlas，以分析 BNIP3 水平与卵巢癌患者的总生存期和无进展生存期之间的相关性。汇总分析表明，较高的 BNIP3 水平与较差的总体生存率相关（95% 置信区间；风险比 = 1.18、1.04–1.34；P = 0.013）和无进展生存期（95% 置信区间；风险比 = 1.26、1.10–1.43 ；P = 0.00049）。然而，个体数据集和组织学分层分析的结果、FIGO (Federation Internationale de Gynecolgie et d'Obstetrique) 分期、化疗方案和 P53 突变状态各不相同。这些发现表明顺铂诱导的细胞凋亡依赖于卵巢癌细胞系中的 BNIP3 水平。因此，靶向 BNIP3 可能是恢复顺铂敏感性的一种潜在方式。

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BNIP3 contributes to cisplatin-induced apoptosis in ovarian cancer cells.

BNIP3 is a proapoptotic protein that mediates apoptosis, necrosis and autophagy. However, the involvement of BNIP3 in cisplatin‐induced apoptosis in ovarian cancer is not clear. In this study, we examined the role of BNIP3 in ovarian cancer during cisplatin treatment and its correlation with clinical outcomes. We first measured cisplatin cytotoxicity and BNIP3 levels before and after cisplatin exposure for ovarian cancer cell lines A2780, SKOV3, OVCAR4, OV2008, ES2 and HO8910. BNIP3 was observed to be differentially expressed in these cell lines, and cisplatin induced a significant increase in BNIP3 levels in A2780 and OVCAR4. BNIP3 knockdown with siRNA in A2780 and OVCAR4 significantly reduced cisplatin cytotoxicity in these two cell lines and alleviated cisplatin‐induced apoptosis. We searched the online databases Gene Expression Omnibus and The Cancer Genome Atlas to analyze the correlation between BNIP3 level and overall survival and progression‐free survival in patients with ovarian cancer. Pooled analyses showed that higher BNIP3 level was correlated with poorer overall survival (95% confidence intervals; hazard ratio = 1.18, 1.04–1.34; P = 0.013) and progression‐free survival (95% confidence intervals; hazard ratio = 1.26, 1.10–1.43; P = 0.00049). However, the results of individual datasets and stratification analyses of histology, FIGO (Federation Internationale de Gynecolgie et d’Obstetrique) stage, chemotherapy regimen and P53 mutation status varied. These findings indicate that cisplatin‐induced apoptosis is dependent on BNIP3 level in ovarian cancer cell lines. Targeting BNIP3 may therefore be a potential way of restoring cisplatin sensitivity.

更新日期：2020-06-27

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