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

  • Discov Oncol. 2025 Jan 3;16(1):3. doi: 10.1007/s12672-024-01723-5.
Liangliang Wang  1 ,  Shanshan Ma  1 ,  Huiwen Su  1 ,  Dandan Nie  1 ,  Lihua Wang  2
Affiliations
  • 1. Department of Oncology and Gynecology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, Anhui, China.
  • 2. Department of Oncology and Gynecology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, Anhui, China. [email protected].
PMID: 39752011 DOI: 10.1007/s12672-024-01723-5
Abstract

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.

Keywords
Fibroblast growth factor 2; Fibroblast growth factor receptor 1; Gemcitabine; Hypoxia-inducible factor 1 alpha; Ovarian cancer; Vascular endothelial growth factor B.
Products