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

Liu, Chuan; Yan, Xu; Wang, Hua-Qin; Gao, Yan-Yan; Liu, Juanjuan; Hu, Zhenhua; Liu, Dawo; Gao, Jian; Lin, Bei

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.

OVARIAN cancer; CANCER cells; PROTEASOME inhibitors; UBIQUITIN; AUTOPHAGY; APOPTOSIS

BMC Cancer, 2012, Vol 12, Issue 1, p622

1471-2407

Academic Journal

10.1186/1471-2407-12-622