Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells

Sun, Yang; Liu, Jia-hua; Jin, Long; Lin, Sai-mei; Yang, Yin; Sui, Yu-xia; Shi, Hong

doi:10.1016/j.canlet.2010.02.001

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Volume 294, Issue 2 , Pages 204-210, 28 August 2010

Over-expression of the Beclin1 gene upregulates chemosensitivity to anti-cancer drugs by enhancing therapy-induced apoptosis in cervix squamous carcinoma CaSki cells

Yang Sun
- Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China
- Corresponding author. Address: Department of Obstetrics and Gynecology, Fujian Provincial Hospital, No. 134, Dong Street, Fuzhou, Fujian 350001, PR China. Tel.: +86 591 83755833; fax: +86 591 87557768.
Jia-hua Liu
- Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China
Long Jin
- Department of Pathology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China
Sai-mei Lin
- Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Provincial Hospital, Fuzhou, Fujian 350001, PR China
Yin Yang
- Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China
Yu-xia Sui
- Department of Pharmacy, Fujian Provincial Hospital, Fuzhou, Fujian 350001, PR China
Hong Shi
- Department of Obstetrics and Gynecology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, Fujian 350001, PR China

Received 15 October 2009; received in revised form 27 January 2010; accepted 1 February 2010. published online 08 March 2010.

Abstract

The purpose of this study was to investigate whether the autophagy-related gene, Beclin1, plays a role in the regulation of chemosensitivity to anti-cancer drugs in cervical cancer CaSki cells. Expression of the Beclin1 protein was up-regulated in pcDNA3.1-Bec transfectants and led to cell arrest in the G₀/G₁ phase of the cell cycle. The MTT assay indicated that over-expression of Beclin1 sensitized CaSki cells to chemotherapeutic drugs (cisplatin, paclitaxel, 5-fluorouracil, and epirubicin) and induced greater degrees of cytotoxicity than vector-only controls. After treatment with anti-cancer drugs, flow cytometric analysis indicated that the Beclin1-transfected group showed a greater increase in apoptosis than did the non-transfected group. Furthermore, pSUPER-Bec transfectants did not lead to a significant increase of resistance to each of these anti-cancer drugs. These results suggest that Beclin1 plays an important role in the regulation of potent anti-tumor activity, and over-expression of Beclin1 in CaSki cells may enhance apoptosis signaling induced by anti-cancer drugs.

Keywords: Autophagy, Apoptosis, Beclin1, Anti-cancer