Abstract 2391: Alterations in metformin mediated metabolism in chemoresistant ovarian cancer cells

Abstract Ovarian cancer (OVCA) is the fifth leading cause of death in post-menopausal women in comparison to all other gynecologic malignancies. Late detection of OVCA is common as screening is done mostly in women over 63. This delay in screening coupled with poor prognosis presents the need for novel treatment measures. Repurposing of Metformin (Met), a biguanide used to increase insulin responses in the body, has been identified as a promising approach for therapeutic treatment in OVCA patients. The purpose of this study is to isolate metabolic pathways used by Met to alter OVCA onset. Preliminary results show that Met inhibits cell proliferation and clonogenic growth in both HeyA8 and HeyA8MDR which are drug-sensitive and drug-resistant cell lines, respectively. In combination with carboplatin, Met treatment enhanced chemosensitivity in both cell lines. In addition, lipidomic analysis was done to monitor the impact of lipid metabolites on OVCA cells. Our analysis showed differences in neutral lipid composition in drug-sensitive and resistant cells which indicates the role of various lipid species play in mediating drug-resistance. Furthermore, Met treatment triggered anti-cancerous pathways through syntheses of lipid metabolites. This data indicates that cell proliferation, along with clonogenic growth are inhibited dose dependently by Met treatment in drug-resistant and drug-sensitive cell lines. Chemosensitivity is enhanced by Met treatment in combination with carboplatin in HeyA8 and HeyA8MDR cell lines. Together, the data suggests that autophagy and lipid biogenesis can be altered through metabolic pathways by Met treatment. Through the use of repurposed Metformin, this approach shows promising results of a treatment regimen and potential prevention of OVCA. Citation Format: Brenita Colette Jenkins, Debarshi Roy, Kristal Maner-Smith, Viji Shridhar. Alterations in metformin mediated metabolism in chemoresistant ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2391.