Overexpression of Bcl-2 partly inhibits apoptosis of human cervical cancerSiHa cells induced by arsenic trioxide

Objective To study the biological effect of arsenic trioxide (As2O3) on hum an cervical cancer SiHa cells and SiHa cells overexpressing bcl-2 gene. Methods SiHa cells with overexpression of Bcl-2 (SiHa-Bcl2 cells) were esta blished by transfecting SiHa cells with Bcl-2 expression vector. The sensit ivities of SiHa and SiHa-Bcl2 cells to As2O3 were determined using MTT (Thi azolyl blue) reduction and colony forming ability assay, morphological anal ysis, flow cytometric analysis, DNA agarose gel electrophoresis, in situ ce ll death detection (TUNEL), Northern blot, RT-PCR and Western blot. Results As2O3 inhibited the growth of SiHa cells and induced G(2)/M arrest and apoptosis of the cells. RT-PCR and Western blot analysis revealed that As2O3 induced SiHa cell apoptosis possibly via inhibiting the expression of HPV16 E7 and decreasing the expression of c-myc. However, we found that Si Ha-Bcl2 cells partly resisted As2O3 induced apoptosis, which might be relat ed to the prevention of the down-regulation of HPV16 E7 and c-myc gene expr ession. Nevertheless, As2O3 at a high concentration could still induce apop tosis of SiHa-Bcl2 cells mainly via decreasing Bcl-2 expression and slightl y inhibiting viral gene expression. Conclusion As2O3 is an inducer of the apoptosis of human cervical carcinoma cells and the cells overexpressing Bcl-2 can partly resist As2O3 induced a poptosis. but the exact mechanism is unclear.