Abstract 5703: NDRG1 enhances cisplatin-induced apoptosis by upregulating BMF in ovarian cancer cells

Abstract Epithelial ovarian cancer (EOC) is the most lethal malignancy of the female reproductive system, with a five-year survival rate of just 32% for patients diagnosed at distant stages, which accounts for over 48% of cases. Although most EOC patients initially achieve a complete response with surgery and chemotherapy, the majority experience relapse, and recurrent tumors often develop resistance to the original drug regimen. Tumor relapse and acquired chemotherapy resistance are primary contributors to the high mortality associated with EOC. Ovarian cancer is a highly heterogeneous disease, exhibiting extensive variability at the molecular, cellular, and clinical levels. This heterogeneity significantly impacts therapeutic responses, particularly to platinum-based chemotherapies such as cisplatin, leading to variable treatment outcomes among patients. To gain deeper insights into the heterogeneity of ovarian cancer cells in response to cisplatin treatment, single-cell RNA sequencing (scRNA-seq) was conducted on spheroid-cultured ovarian cancer cells exposed to cisplatin. Following a two-week treatment period and a subsequent two-week recovery phase, several distinct clusters of cisplatin-surviving ovarian cancer cells were identified, exhibiting enhanced growth advantages. Analysis of the gene expression profiles of the cell clusters revealed that N-myc downstream regulated 1 (NDRG1) is highly expressed in clusters eliminated by cisplatin, whereas its expression is significantly lower in clusters that survive cisplatin treatment. Further investigation demonstrated that NDRG1 plays a critical role in promoting cisplatin-induced apoptosis. RNA sequencing of NDRG1-knockdown cells identified Bcl2 Modifying Factor (BMF) as a downstream target positively regulated by NDRG1. Given that BMF can bind to Bcl2 protein and functions as an apoptotic activator, these findings suggest that ovarian cancer cells with high NDRG1 expression are more susceptible to cisplatin-induced apoptosis due to NDRG1-mediated upregulation of BMF. Citation Format: Yajing Yang, Ananya Banerjee, Linzhou Wang, Na Li, Patrick Stevens, Elsa Wani, Jessica Miao, Aidan Li, Xiaoli Zhang, Qi-En Wang. NDRG1 enhances cisplatin-induced apoptosis by upregulating BMF in ovarian cancer cells [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 5703.