Abstract 1274: Heterotrimeric stimulatory GTP-binding proteins inhibit cisplatin-induced apoptosis by inducing XIAP in cervical cancer cells

Abstract

Abstract Cisplatin (cis-dichlorodiammineplatinum (II)) induces DNA double-strand breaks (DSBs), which are considered as the main cytotoxic damage that induces apoptosis of human cancer cells. Cisplatin was also known to found to inhibit DNA-synthesis and DNA-repair in HeLa cervical carcinoma cells. Recently, we observed that heterotrimeric G proteins modulate apoptosis signaling in several cancer cell lines. In this study, we attempted to investigate the effect of Gαs on apoptosis triggered by cisplatin and its molecular mechanism in HeLa cells. Expression of constitutively active Gαs (GαsQL) decreased the cleavage of caspase-3 and PARP at 24 hr after treatment of HeLa cells with 30 µM cisplatin, indicating that Gαs inhibited cisplatin-induced apoptosis of HeLa cells. Expression of GαsQL increased the expression of XIAP (inhibitor of apoptosis protein), and partially recovered the cisplatin-induced decrease in XIAP. Knock down of Gαs expression by shRNA reduced the expression of XIAP and augmented cisplatin-induced apoptosis. This study shows that Gαs can protect apoptosis triggered by cisplatin by up-regulation of XIAP in HeLa cervical cancer cells. These results suggest that Gαs signaling may contribute carcinogenesis and progression of cervical cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1274.