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

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 G(0)/G(1) 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.