Abstract 334: Glucose regulates chemoresistance and stemness via Wnt/β-catenin signaling in ovarian cancer cells

Abstract

Abstract Glucose metabolic alteration is one of the hallmarks of ovarian cancer. Here, we first demonstrated the function of glucose as a signature molecule that regulated chemosensitivities in ovarian cancer cells. To verify the role of glucose on the chemoresistance in ovarian cancer cells, we used various concentrations of glucose containing media (0 mM to 20 mM). Glucose reduction inhibited proliferation of various ovarian cancer cell types; irrespective of p53 status and cisplatin (CDDP) sensitivities. Interestingly, CDDP (10 to 20 μM) induced apoptosis were increased and expressions of p-glycoprotein (multidrug resistance protein 1, MDR1) and ABCG2 (ATP-binding cassette sub-family G member 2) were decreased in both mRNA and protein levels by glucose free conditions. Moreover, sphere forming capacities and stemness related gene expressions, SOX2, OCT4, BMI1 and Nanog, were also decreased in ovarian cancer cells in response to glucose starvation. Suppression of CDDP resistance and stemness in ovarian cancer was found to be associated with the activation of GSK3β in response to limitation of glucose availabilities, as confirmed by the function of the GSK3β inhibitors (LiCl and SB SB216763) and also downstream molecules, β-catenin and cyclin D1. In contrast, high glucose (20 mM) environment enhanced CDDP resistance in ovarian cancer cells via elevation of p-glycoprotein and ABCG2 expressions, sphere forming capacities and stemness related gene expressions. Moreover, CDDP (10 to 20 μM) in high concentration of glucose media induced apoptotic cell death were significantly decreased. This study described the novel function of glucose in chemoresistance in ovarian cancer cells by deregulation of multidrug efflux pumps and stemness through Wnt/ β-catenin signaling cascades. Citation Format: HyeRan Gwak, Soochi Kim, UnTek Jo, Yong Sang Song. Glucose regulates chemoresistance and stemness via Wnt/β-catenin signaling in ovarian cancer cells. [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 334. doi:10.1158/1538-7445.AM2015-334