Abstract 2134: Cyclosporin-A enhances cisplatin induced-apoptosis through inhibition PPIase activity of cyclophinlin A and Akt signaling pathway in a human tongue squamous cell carcinoma

Abstract

Abstract Purpose: Chemoresistance is a serious problem in squamous cell carcinoma of the tongue, but the mechanism of resistance and strategies against the resistance have not been elucidated. Cyclosporin-A (CsA), an immunosuppressive drug that targets calcineurin and cyclophilin A (CypA), rencent studies show that it enhances apoptosis of chemotherapeutic drugs in various kinds of tumors. The aim of our study was to investigate whether CsA could enhance cisplatin induced apoptosis in tongue carcinoma. Methods: In the present study, we examined the effect of cisplatin and CsA, individually or in combination in a human tongue squamous cell carcinoma cell line. Tumor cell growth, cell cycle, cell apoptosis, PPIase activity of cyclophinlin A and Akt phosphorylation were examined. Results: A combination of cisplatin with CsA synergistically attenuates cell gowth viability and markedly increased cleavage of caspase-3 and cytoplasmic histone associated DNA fragments in tongue squamous cell carcinoma cells, compared with single-agent treatment alone. Moreover, anti-apoptotic proteins p53 and Bax/Bcl-2 ratio were significantly increased in the combination therapy group. In contrast, the PPIase activity of cyclophinlin A and Akt phosphorylation were evidently decreased by the combination effect. Conclusion: Together, our data suggest that CypA and Akt signaling pathway play a key role in cisplatin resistance of the tongue carcinoma cells. The combination therapy with cisplatin and CSA can overcome the chemoresistance of cisplatin, this may be a potentially useful therapeutic option for the human tongue squamous cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2134. doi:10.1158/1538-7445.AM2011-2134