The molecular mechanism of gemcitabine in inhibiting the HIF-1α/VEGFB/FGF2/FGFR1 signaling pathway for ovarian cancer treatment

• DOI: 10.1007/s12672-024-01723-5
• Publication Date: 2025-01-03T06:36:25Z
• Authors: Liangliang Wang; Shanshan Ma; Huiwen Su; Dandan Nie; Lihua Wang
• Keywords: Hypoxia-inducible factor 1 alpha; Ovarian cancer; Vascular endothelial growth factor B; Research; Fibroblast growth factor 2; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Gemcitabine; Fibroblast growth factor receptor 1; RC254-282

Ovarian cancer is a common malignant tumor in women, exhibiting a certain sensitivity to chemotherapy drugs like gemcitabine (GEM). This study, through the analysis of ovarian cancer single-cell RNA sequencing (scRNA-seq) data and transcriptome data post-GEM treatment, identifies the pivotal role of hypoxia-inducible factor 1 alpha (HIF-1α) in regulating the treatment process. The results reveal that HIF-1α modulates the expression of VEGF-B, thereby inhibiting the fibroblast growth factor 2 (FGF2)/FGFR1 signaling pathway and impacting tumor formation. In vitro experiments validate the mechanistic role of HIF-1α in GEM treatment, demonstrating that overexpression of HIF-1α reverses the drug's effects on ovarian cancer cells while silencing fibroblast growth factor receptor 1 (FGFR1) can restore treatment efficacy. These findings provide essential molecular targets and a theoretical foundation for the development of novel treatment strategies for ovarian cancer in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-024-01723-5.