Inhibition of autophagy sensitizes MDR-phenotype ovarian cancer SKVCR cells to chemotherapy

Publication date: August 2016
Source:Biomedicine & Pharmacotherapy, Volume 82
Author(s): Bing Liang, Xiaodong Liu, Yang Liu, Dejuan Kong, Xiaomei Liu, Rui Zhong, Shumei Ma
Autophagyis 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.Chemoresistanceis a major challenge in the clinical treatment of ovarian cancer, of which the underlying mechanisms remain unknown.ObjectiveThe aim of the present study was to explore the role of autophagy in vincristine (VCR) resistant ovarian cancer cells.MethodsThe 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.ResultsCompared 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.ConclusionsOur 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.



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