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The different regulatory effects of p53 status on multidrug resistance are determined by autophagy in ovarian cancer cells.
MedLine Citation:
PMID:  22564245     Owner:  NLM     Status:  Publisher    
PURPOSE: Multidrug resistance (MDR) has become an obstacle for chemotherapy of cancer. p53 is reported to participate in the regulation of MDR, but the association between p53 status and MDR are complicated and conditional. It has been verified that apoptosis is not the only mechanism for MDR regulation by p53, the roles of autophagy in MDR is less studied. PATIENTS AND METHODS: Human ovarian carcinoma cell lines SKOV3 and multidrug resistant phenotype SKVCR cells were used and wild-type p53 (wt p53) and mutant 175H constructs were introduced into cells to establish cell models with different p53 status by gene engineering, the sensitivity to vincristine (VCR), cisplatin (DDP), pirarubicin (THP) and etoposide (VP-16) were detected by MTT assay, Western blot and quantitative real-time PCR were used to detect the expression of protein and mRNA, especially, monodansylcadaverine (MDC) staining was used for autophagy rate, Hoechst 33342/propidium iodide (PI) were used to assess apoptosis and necrosis. RESULTS: SKVCR cells induced by VCR shown overexpression of P-glycoprotein (P-gp) and MDR, and also displayed an enhanced autophagy compared with parental SKOV3. Wt p53 and 175H has no influence on drug sensitivity in SKOV3, while both sensitized SKVCR cells to VCR, THP and VP-16, especially 175H. The introduction of wt p53-induced apoptosis only, while 175H trigged autophagic cell death, necrosis and apoptosis so as to reverse the MDR. CONCLUSION: The enhancement of autophagy in MDR cells allows to survive during chemotherapy stress, autophagy plays important role in wt p53 and mutant p53-immediated MDR. The different influence of p53 status on drug sensitivity hint the individual treatment strategies based on p53 status in patients.
Dejuan Kong; Shumei Ma; Bing Liang; Heqing Yi; Yinlong Zhao; Rui Xin; Li Cui; Lili Jia; Xin Liu; Xiaodong Liu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-17
Journal Detail:
Title:  Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie     Volume:  -     ISSN:  1950-6007     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-5-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8213295     Medline TA:  Biomed Pharmacother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, 130021 Changchun, PR China.
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