Panoply™ Human HIF1A Over-expressing Stable Cell Line

Ovarian cancer is a common malignancy in women that exhibits sensitivity to chemotherapeutic agents such as gemcitabine (GEM). In this study, researchers analyzed single-cell RNA sequencing (scRNA-seq) data and post-GEM treatment transcriptomic data from ovarian cancer samples, revealing the pivotal role of hypoxia-inducible factor 1α (HIF-1α) in regulating the response to this therapy. The results demonstrated that HIF-1α influences tumor formation by modulating VEGF-B expression, which in turn inhibits the fibroblast growth factor 2 (FGF2)/FGFR1 signaling pathway. In vitro experiments validated the mechanism of HIF-1α action during GEM treatment: HIF-1α overexpression reversed the drug's effects on ovarian cancer cells, whereas silencing fibroblast growth factor receptor 1 (FGFR1) restored therapeutic efficacy. These findings provide important molecular targets and a theoretical basis for the future development of novel therapeutic strategies for ovarian cancer.

Western blot analysis revealed that the expression levels of HIF-1α and VEGF-B were significantly higher in SK-OV-3 ovarian cancer cells compared to ISOE-80 cells. Furthermore, compared to untreated SK-OV-3 cells, the expression levels of HIF-1α, VEGF-B, FGF2, and FGFR1 were significantly reduced in GEM-treated SK-OV-3/GEM cells (Figures 1A, B). To investigate the role of HIF-1α in GEM treatment, SK-OV-3 ovarian cancer cells were divided into the following groups: a GEM-treated group (GEM), an overexpression negative control group (oe-NC + GEM), an HIF-1α overexpression group (oe-HIF-1α + GEM), and an HIF-1α overexpression combined with FGFR1 silencing group (oe-HIF-1α + sh-FGFR1 + GEM). Western blot analysis showed that the expression levels of HIF-1α, VEGF-B, FGF2, and FGFR1 were reduced in the GEM-treated group compared to the control group. In the oe-HIF-1α + GEM group, the expression levels of these proteins increased, whereas silencing FGFR1 resulted only in a decrease in FGFR1 expression (Figures 1C, D). CCK-8 assay results demonstrated that GEM treatment inhibited cell proliferation compared to the control group; HIF-1α overexpression promoted cell proliferation compared to the oe-NC + GEM group, whereas silencing FGFR1 significantly inhibited this effect (Figure 1E).

Figure 1. GEM can significantly reduce ovarian cancer cell proliferation by inhibiting the HIF-1α/VEGF-B/FGF2/FGFR1 signaling pathway. (Wang L, et al., 2025)