Inhibition of autophagy sensitizes MDR-phenotype ovarian cancer SKVCR cells to chemotherapy
Inhibition of autophagy sensitizes MDR-phenotype ovarian cancer SKVCR cells to chemotherapy
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抑制自噬使多药耐药表型卵巢癌 SKVCR 细胞对化疗敏感
DOI：
10.1016/j.biopha.2016.04.054
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发表时间：
2016-08-01
影响因子：
7.5
通讯作者：
Ma, Shumei
中科院分区：
文献类型：
--
作者：
Liang, Bing;Liu, Xiaodong;Ma, Shumei
自噬：是一种细胞内溶酶体降解途径，其主要功能是使细胞在应激条件下存活。自噬是一把双刃剑，既可以促进细胞存活，也可以促进细胞死亡，化疗耐药是卵巢癌临床治疗的主要挑战，其机制尚不清楚。目的：探讨自噬在卵巢癌长春新碱（VCR）耐药细胞中的作用。使用SKOV 3亲本细胞系和SKVCR，VCR抗性卵巢癌细胞。3-MA（3-甲基腺嘌呤）和CQ（氯喹）也被用作自噬抑制剂。采用CCK-8检测细胞活力，实时荧光定量PCR和Western blot检测mRNA和蛋白表达，MDC染色和流式细胞术检测细胞自噬和凋亡。SKVCR细胞的自噬水平高于SKOV 3细胞，3-MA和CQ可抑制SKVCR细胞的自噬。在SKVCR细胞中，VCR进一步增加凋亡水平，3-MA和CQ抑制自噬并增强VCR的细胞毒性。3-MA和CQ可通过增强VCR诱导的细胞毒作用克服SKVCR细胞获得性耐药，并促进细胞凋亡。结论：自噬对多药耐药SKVCR细胞具有保护作用。自噬的抑制通过增加细胞凋亡和抑制自噬来增加VCR的杀伤作用，这表明了治疗耐药SKVCR细胞的更好策略。(C)2016 Elsevier Masson SAS。All rights reserved.
Autophagy: is an intracellular lysosomal degradation pathway where its primary function is to allow cells to survive under stressful conditions. Autophagy is, however, a double-edge sword that can either promote cell survival or cell death.Chemoresistance: is a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown.Objective: The aim of the present study was to explore the role of autophagy in vincristine (VCR) resistant ovarian cancer cells.Methods: The SKOV3 parental cell line and SKVCR, the VCR-resistant ovarian carcinoma cells were used. 3-MA (3-Methyladenine) and CQ (Chloroquine) were also used as autophagy inhibitors. CCK8 (Cell Counting Kit-8) was used to detect cell viability, quantitative real-time PCR and Western blot were used to detect the expressions of mRNA and protein, MDC staining and flow cytometry were used to detect autophagy and apoptosis, respectively.Results: Compared with parental SKOV3 cells, SKVCR cells showed Multidrug Resistance (MDR). SKVCR cells demonstrated higher autophagy levels than SKOV3 cells, which could be inhibited by 3-MA and CQ. In SKVCR cells, VCR increased apoptosis levels further, 3-MA and CQ inhibited autophagy and potentiated the cytotoxicity by VCR. Moreover, 3-MA and CQ overcame the acquired VCR resistance in SKVCR cells by enhancing VCR-induced cytotoxicity, and promote apoptosis.Conclusions: Our data indicate that autophagy has a protective role in the multi-drug resistant SKVCR cells. The inhibition of autophagy increases the killing effects of VCR by increasing apoptosis and inhibiting autophagy, suggesting a better strategy for the treatment of drug-resistant SKVCR cells. (C) 2016 Elsevier Masson SAS. All rights reserved.