Abstract 3474: GDF15 as a serum marker of cisplatin response in ovarian cancer cells.

Abstract

Abstract Ovarian cancer treatment consists of surgery followed by a chemotherapy combination entailing a platinum agent (cisplatin/carboplatin) and a taxane (paclitaxel). While 70-80% of patients initially respond to the standard treatment, the majority will relapse, and of these patients, 70-90% die because of drug resistance. Therefore, identifying markers that can predict therapeutic response and/or therapeutic targets is of great interest. To identify genes involved in chemoresistance, a microarray study of an ovarian cancer cell line (A2780) treated with varying doses of cisplatin and at varying time points was conducted. This study showed GDF15 had the highest fold-induction by cisplatin treatment. GDF15 induction by cisplatin was further validated by RT-PCR and Western blot analysis in the A2780 and 12 other cell lines with varying sensitivity/resistance to cisplatin. To further test whether GDF15 plays a role in cisplatin resistance, we knocked down its expression by esiRNA. GDF15 knockdown revealed an increase in the cisplatin IC50, suggesting that GDF15 sensitizes ovarian cancer cells to cisplatin. To determine whether GDF15 was also induced in vivo we injected mice intraperitoneally with either A2780 (cisplatin sensitive) or RMG1 (cisplatin resistant) cells. Once the tumors developed, the mice were treated with either 2.5 mg/kg or 5 mg/kg cisplatin and both the tumors and sera collected 24 and 48 hours after treatment. ELISA results on the serum showed an increase in GDF15 in mice after cisplatin treatment. Although there was no correlation between the two cisplatin doses used and GDF15 there was a correlation between GDF15 and tumor weight. Thus, our results suggest that GDF15 is induced by cisplatin both in vitro and in vivo and has a potential role as a serum biomarker to predict chemotherapeutic response. Citation Format: Daisy I. Izaguirre, Suet Yan Kwan, Zhifei Zu, Yvonne T. Tsang-Lee, Kwong-Kwok Wong. GDF15 as a serum marker of cisplatin response in ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3474. doi:10.1158/1538-7445.AM2013-3474