ABS 049: Inhibition of Drug Efflux Modulates Lipid Metabolism and Enhances Paclitaxel Sensitivity in Chemoresistant Ovarian Cancer

Phillip Park ¹ ³, Basel White ² ³, Dr. Deepraj Ghosh¹ ³, Dr. Michelle Dawson ¹ ² ³

¹ Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University
² Institute for Biology, Engineering, and Medicine, Brown University
³ Legorreta Cancer Center, Brown University

The Van Wickle Journal (2026) Volume 2, ABS049

Introduction: High grade serous ovarian carcinoma (HGSOC) is the most lethal and common epithelial ovarian cancer subtype with a 5-year survival rate around 30%. Paclitaxel (PTX) — a microtubule-stabilizing agent that induces mitotic arrest and apoptosis — is one of the most widely used therapeutics for HGSOC. However, recurrence due to chemoresistance occurs in 70-80% of patients, highlighting the need for new therapeutic strategies. One emerging approach is to target lipid metabolism in cancer cells. To survive chemotherapy, cancer cells exhibit metabolic plasticity to meet the energetic demands of resistance. Lipid droplet (LD) accumulation is a hallmark cancer phenotype, supplying fatty acids for oxidation and mitochondrial respiration. In this study, we investigated the connection between ATP-cassette transporters, upregulated in chemotherapy resistance to increase drug efflux, and lipid metabolism in HGSOC. We used verapamil (VP), a Ca2+ channel inhibitor, to inhibit drug efflux in our PTX-Sensitive (TS) and PTX-Resistant HGSOC cell lines. Cells were treated with PTX, VP, or in combination. We performed single-cell immunofluorescent analysis of nuclear and cellular morphology, LD accumulation, and mitochondrial alterations. Our results demonstrate LD accumulation was markedly increased in TS cells upon PTX, while TR cells remained viable, suggesting toxicity-associated LD accumulation in TS cells. TR cells have higher LD levels than TS cells that are further enhanced with VP treatment. When combined with PTX, VP enhanced PTX sensitivity, reflected by altered nuclear/tubulin morphology and decreased viability. Additionally, mitochondrial intensity, quantified by TOMM20 immunofluorescence (a marker of the outer mitochondrial membrane), was significantly elevated upon VP treatment in TR cells, indicating mitochondrial reprogramming. Our findings suggest that VP may enhance PTX efficacy by inhibiting drug efflux while altering lipid metabolism and mitochondrial dynamics, identifying metabolic reprogramming as a target to resensitize treatment-resistant HGSOC.