Abstract 1002: Fatty acid synthase is overexpressed in Middle Eastern epithelial ovarian carcinoma (EOC) and its inhibition potentiates cisplatin-mediated apoptosis in EOC cells

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of fatty acids has been shown to be deregulated in several cancers including epithelial ovarian carcinoma (EOC). In this study, we investigated the function of Fatty acid Synthase (FASN) signaling pathway in a large series of middle eastern EOC patient samples, using a panel of cell lines, and nude mouse model. Using immunohistochemistry, we detected FASN in 75.5 %(114/151) tumor samples. Overexpression of FASN was significantly associated with tumor proliferative marker Ki-67 (p=0.0009), activated AKT (p=0.0117) and XIAP(p=0.0046). Treatment of EOC cell lines with C75 a selective inhibitor of FASN causes inhibition of EOC cell proliferation via induction of apoptosis. Inhibition of FASN by C75 led apoptosis via involving mitochondrial pathway, activation of caspases and downregulation of XIAP, and survivin. FASN inhibition causes down regulation of activated AKT. In addition, inhibition by FASN siRNA causes downregulation of FASN and activation of caspases suggesting the role of FASN in C75 mediated apoptosis. Furthermore, treatment of EOC cells with subtoxic doses C75 augmented the effect of cisplatin mediated inhibition of cell proliferation and induction of apoptosis. Finally, treatment of EOC cell line xenografts with combination of C75 and cisplatin resulted in growth inhibition of tumors in nude mice through downregulation of FASN and activation of caspases Altogether, our results suggest that overexpression of FASN in Middle eastern EOC suggests that FASN may be a potential therapeutic target in a subset of EOC, alone or in combination with other conventional chemotherapeutic agents. 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 1002. doi:10.1158/1538-7445.AM2011-1002