title: Inhibition of autophagy sensitizes MDR-phenotype ovarian cancer SKVCR cells to chemotherapy.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology Care, School of Nursing, Jilin University, Changchun 130021, China; Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
authors.affiliation: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Center for Radiological Research, Changchun, 130021, China; Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pediatric Ultrasound, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Dejuan
authors.initials: D
authors.lastname: Kong
authors.affiliation: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, China. Electronic address: shmm2001@126.com.
authors.forename: Shumei
authors.initials: S
authors.lastname: Ma
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D010641:Phenotype; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014750:Vincristine
keywords: Autophagy; Chemosensitivity; Multidrug resistance; Ovarian cancer; Vincristine