Abstract 697: c-MET as a potential target in ovarian clear-cell carcinoma

Abstract

Abstract Purpose: Recent reports revealed that c-MET activation is associated with epithelial ovarian carcinoma (EOC) and is association with poor prognosis. In this study, we investigated the effects of therapeutic targeting for c-MET in ovarian clear cell carcinoma (OCCC). Experimental Design: Expression levels of c-MET in the epithelial ovarian carcinomas and normal ovarian tissues were evaluated using real-time PCR. To test c-MET inhibitors in CCC cell lines, we performed in vitro experiments including MTT and apoptosis assay. We performed Western blots to evaluate the c-MET expression and down-stream pathway. In addition, we performed in vivo therapy experiments in orthotopic ovarian cancer mice model (RMG1) and patient-derived tumor xenograft (PDX) models of CCC to confirm these effects. Results: The c-MET expression was significantly increased in CCCs compared with serous carcinomas and normal ovarian tissues (P < 0.05). CCC cells treated with c-MET inhibitors (SU11274 or crizotinib) demonstrated significantly decreased cell viability and increased apoptosis. Western blot assay showed that the protein expressions for c-MET signaling pathway were decreased by c-MET inhibitor. Moreover, tumor weight was significant decreased in both in vivo RMG1 and PDX models receiving SU11274 treatment compared with control (P < 0.05). Conclusion: These results show that c-MET inhibitor has the significant anti-tumor effects in ovarian CCC, and suggested that c-MET could have the potential agent in the therapy for this cancer. Citation Format: Jeong-Won Lee, Byoung-Gie Kim, Duk-Soo Bae, Yoo Young Lee. c-MET as a potential target in ovarian clear-cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 697. doi:10.1158/1538-7445.AM2015-697