Autophagy-independent enhancing effects of Beclin 1 on cytotoxicity of ovarian cancer cells mediated by proteasome inhibitors

BMC Cancer

Research Article

Hua-Qin Wang¹  Yan-Yan Gao¹  Juanjuan Liu²  Chuan Liu²  Zhenhua Hu²  Bei Lin²  Dawo Liu²  Jian Gao²  Xu Yan³ 

[1] Department of Biochemistry & Molecular Biology, China Medical University, 110001, Shenyang, China;Department of Obstetrics & Gynecology, Shengjing Hospital Affiliated to China Medical University, 110004, Shenyang, China;Department of Prosthodontics, School of Stomatology, China Medical University, 110001, Shenyang, China;

关键词: Proteasome inhibition;    Beclin1;    Ovarian cancer;   

DOI  :  10.1186/1471-2407-12-622

 received in 2012-07-04, accepted in 2012-12-17,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe ubiquitin-proteasome system and macroautophagy (hereafter referred to autophagy) are two complementary pathways for protein degradation. Emerging evidence suggests that proteasome inhibition might be a promising approach for tumor therapy. Accumulating data suggest that autophagy is activated as a compensatory mechanism upon proteasome activity is impaired.MethodAutophagy activation was measured using acridine orange staining and LC3 transition. Cell viability and apoptosis were measured using MTT assay and flow cytometry, respectively. Beclin 1 expression vectors or shRNA against Beclin 1 (shBeclin 1) were transfected to investigate the role of Beclin 1 in autophagy activation and cytotoxicity of ovarian cancer cells induced by proteasome inhibitors.ResultsProteasome inhibitors suppressed proliferation and induced autophagy in ovarian cancer cells. Neither phosphoinositide 3-kinase (PI3K) inhibitors nor shRNA against Beclin 1 could abolish the formation of acidic vacuoles and the processing of LC3 induced by proteasome inhibitors. Moreover, Beclin 1 overexpression enhanced anti-proliferative effects of proteasome inhibitors in ovarian cancer cells.ConclusionsFor the first time, the current study demonstrated that proteasome inhibitors induced PI3K and Beclin 1-independent autophagy in ovarian cancer cells. In addition, this study revealed autophagy-independent tumor suppressive effects of Beclin 1 in ovarian cancer cells.

【 授权许可】

Unknown   
© Liu et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.