Overexpression of Bcl-2 partly inhibits apoptosis of human ce rvical cancer SiHa cells induced by arsenic trioxide

Objective To study the biological effect of arsenic trioxide (As(2)O(3)) on human cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. Methods SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were established by transfecting SiHa cells with Bcl-2 expression vector. The sensitivities of SiHa and SiHa-Bcl2 cells to As(2)O(3) were determined using MTT (Thiazolyl blue) reduction and colony forming ability assay, morphological analysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ cell death detection (TUNEL), Northern blot, RT-PCR and Western blot. Results As(2)O(3) inhibited the growth of SiHa cells and induced G2]/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As(2)O(3) induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that SiHa-Bcl2 cells partly resisted As(2)O(3) induced apoptosis, which might be related to the prevention of the down-regulation of HPV16 E7 and c-myc gene expression. Nevertheless, As(2)O(3) at a high concentration could still induce apoptosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightly inhibiting viral gene expression.Conclusion As(2)O(3) is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As(2)O(3) induced apoptosis, but the exact mechanism is unclear.