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Open Access Highly Accessed Research article

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

Chuan Liu1, Xu Yan2, Hua-Qin Wang3, Yan-Yan Gao3, Juanjuan Liu1, Zhenhua Hu1, Dawo Liu1, Jian Gao1 and Bei Lin1*

Author affiliations

1 Department of Obstetrics & Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, 110004, China

2 Department of Prosthodontics, School of Stomatology, China Medical University, Shenyang, 110001, China

3 Department of Biochemistry & Molecular Biology, China Medical University, Shenyang, 110001, China

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Citation and License

BMC Cancer 2012, 12:622  doi:10.1186/1471-2407-12-622

Published: 27 December 2012

Abstract

Background

The 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.

Method

Autophagy 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.

Results

Proteasome 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.

Conclusions

For 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.

Keywords:
Proteasome inhibition; Beclin1; Ovarian cancer