Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells.
Induction of autophagy contributes to cisplatin resistance in human ovarian cancer cells.
复制标题
自噬的诱导导致人卵巢癌细胞对顺铂产生耐药性。
DOI：
10.3892/mmr.2014.2671
复制
发表时间：
2015-01
影响因子：
3.4
通讯作者：
Yi X
中科院分区：
文献类型：
--
作者：
Bao L;Jaramillo MC;Zhang Z;Zheng Y;Yao M;Zhang DD;Yi X
顺铂耐药是卵巢癌临床治疗中的一个主要挑战，其潜在机制尚不清楚。本研究旨在探讨自噬在卵巢癌细胞顺铂耐药中的作用。A2780 cp顺铂耐药卵巢癌细胞和A2780亲本细胞系在本研究中用作模型。使用水溶性四唑盐-8测定法测定细胞活力，并进行蛋白质印迹分析以测定微管相关蛋白1轻链3（LC 3 I和LC 3 II）和Beclin 1的蛋白质表达水平。使用Beclin 1小干扰（si）RNA和3-甲基腺嘌呤（3-MA）来确定自噬的抑制是否可以使顺铂抗性细胞对顺铂重新敏感。透射电镜观察自噬体超微结构，流式细胞仪检测细胞凋亡。在A2780 cp和A2780细胞中，顺铂诱导自噬体的形成，并上调自噬蛋白标志物LC 3 II和Beclin 1的表达水平。然而，A2780 cp细胞中的自噬水平显著高于A2780细胞。顺铂与自噬抑制剂3-MA联合应用，与顺铂单独应用相比，增加了A2780 cp细胞的死亡率，但对细胞凋亡无影响。然而，通过siRNA敲低Beclin 1表达来抑制自噬增强了顺铂诱导的细胞死亡和凋亡。本研究的结果表明，自噬在人卵巢癌细胞中具有保护作用，靶向自噬可能会提高化疗敏感性。
Cisplatin resistance is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown. The aim of the present study was to explore the role of autophagy in cisplatin resistance in ovarian cancer cells. A2780cp cisplatin-resistant ovarian carcinoma cells and the A2780 parental cell line, were used as a model throughout the present study. The cell viability was determined using a water soluble tetrazolium salt-8 assay, and western blot analysis was performed to determine the protein expression levels of microtubule-associated protein 1 light chain 3 (LC3 I and LC3 II), and Beclin 1. Beclin 1 small interfering (si)RNA and 3-methyladenine (3-MA) were used to determine whether inhibition of autophagy may re-sensitize cisplatin-resistant cells to cisplatin. The ultrastructural analysis of autophagosomes was performed using transmission electron microscopy, and apoptosis was measured by flow cytometry. In both A2780cp and A2780 cells, cisplatin induced the formation of autophagosomes and upregulated the expression levels of autophagy protein markers, LC3 II and Beclin 1. However, the levels of autophagy were significantly higher in A2780cp cells, as compared with the A2780 cells. The combined treatment of cisplatin with 3-MA, the autophagy pharmacological inhibitor, increased the cell death rate, but had no effects on apoptosis, as compared with cisplatin treatment alone in A2780cp cells. However, inhibition of autophagy by siRNA knockdown of Beclin 1 expression enhanced cisplatin-induced cell death and apoptosis. The findings of the present study suggest that autophagy has a protective role in human ovarian cancer cells, and that targeting autophagy may promote chemotherapeutic sensitivity.
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影响因子：
13.3
作者：
Carew, Jennifer S.;Nawrocki, Steffan T.;Cleveland, John L.
通讯作者：
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影响因子：
6.6
作者：
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影响因子：
78.5
作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
21.1
作者：
Zhu, Yushan;Zhao, Lixia;Chen, Quan
通讯作者：
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