Abstract 6802: RLIP depletion promotes apoptosis in ovarian cancer

Abstract Ral interacting protein (RLIP) is a multifunctional protein localized and distributed in the plasma membrane, cytosol, and nucleus of the cell. RLIP is ubiquitously expressed in various tissues, including the ovary. In tumorigenesis, RLIP emerges as a common feature for solid tumor growth. RLIP is an anti-apoptotic non-ABC glutathione (GSH)-conjugate transporter involved in receptor-ligand endocytosis, as well as in multispecific drug transport and resistance. The presence of RLIP appears to be indispensable for cancer cells as indicated by its overexpression in various malignant cell lines. Partial inhibition and or depletion of RLIP using antibodies or antisense in the absence of chemotherapy drug causes apoptosis in multiple ovarian cancer (OC) cell lines; in the presence of carboplatin, marked synergy is observed in vitro as well as in vivo. These findings indicate that RLIP is a good target for cancer cell killing, and that its down-regulation would promote apoptosis through both drug-dependent and drug-independent effects. To examine the effect of specific RLIP depletion on apoptosis, we tested the effect of RLIP antisense in a number of OC cell lines. Growth inhibition and apoptosis were observed in all cases upon RLIP depletion. Cytotoxic synergy between RLIP antisense, RLIP antibodies, and carboplatin was examined in cell culture and xenografts of OVCAR8 OC cells. RLIP inhibition by antibodies was equally as effective as antisense and enhanced carboplatin efficacy in OC xenografts. Taken together, these results show that RLIP is a rational and promising new target for OC therapy. (This work was supported in part by the Department of Defense grant W81XWH-22-1-0331. Funding from the Beckman Research Institute of City of Hope is also acknowledged). Citation Format: Sharad S. Singhal, Madhu Krishna, Prakash Kulkarni, David Horne, Ravi Salgia. RLIP depletion promotes apoptosis in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6802.