Introduction: Multidrug resistance (MDR) remains a major obstacle in the treat-ment of epithelial ovarian cancer (EOC). This study aimed to elucidate the regulatory role of FBXW7 in modulating the HSF-1/P-glycoprotein (P-gp) signalling axis and its impact on MDR in ovarian cancer. Materials and Methods: Quantitative PCR, western blotting, immunohistochemistry, and im-munofluorescence were employed to assess FBXW7, HSF-1, and P-gp expression in ovarian tissues and cell lines. Functional assays, including CCK-8 proliferation assays and lentiviral-mediated gene modulation, were conducted in SKOV3 and cisplatin-resistant SKOV3/DDP cells to evaluate the effects of FBXW7 on cell proliferation and drug resistance-associated pathways. Results: FBXW7 expression was markedly reduced in ovarian cancer tissues compared to normal controls and positively correlated with patient progression-free survival. Overexpres-sion of FBXW7 suppressed proliferation in both SKOV3 and SKOV3/DDP cells and led to decreased HSF-1 and P-gp expression. Conversely, FBXW7 knockdown enhanced cell prolif-eration and upregulated the HSF-1/P-gp axis. Immunohistochemical and immunofluorescence analyses confirmed an inverse expression pattern between FBXW7 and HSF-1 in patient tis-sues. Discussion: The findings revealed FBXW7 to suppress multidrug resistance in ovarian cancer by downregulating the HSF-1/P-gp axis, thereby enhancing chemosensitivity. This study has highlighted a novel regulatory mechanism and suggested that restoring FBXW7 function may offer therapeutic benefit in overcoming chemoresistance. Conclusion: FBXW7 acts as a tumour suppressor that mitigates MDR in ovarian cancer by negatively regulating the HSF-1/P-gp pathway. The findings have offered mechanistic insights into chemoresistance and highlight the therapeutic potential of targeting FBXW7-HSF-1 sig-nalling in EOC management.
Yang et al. (Mon,) studied this question.