Wang Liangliang, Ma Shanshan, Su Huiwen, Nie Dandan, Wang Lihua
Department of Oncology and Gynecology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, Anhui, China.
Discov Oncol. 2025 Jan 3;16(1):3. doi: 10.1007/s12672-024-01723-5.
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.
卵巢癌是女性常见的恶性肿瘤，对吉西他滨（GEM）等化疗药物表现出一定的敏感性。本研究通过分析卵巢癌单细胞RNA测序（scRNA-seq）数据和GEM治疗后的转录组数据，确定了缺氧诱导因子1α（HIF-1α）在调节治疗过程中的关键作用。结果显示，HIF-1α调节血管内皮生长因子B（VEGF-B）的表达，从而抑制成纤维细胞生长因子2（FGF2）/成纤维细胞生长因子受体1（FGFR1）信号通路并影响肿瘤形成。体外实验验证了HIF-1α在GEM治疗中的作用机制，表明HIF-1α的过表达可逆转药物对卵巢癌细胞的作用，而沉默成纤维细胞生长因子受体1（FGFR1）可恢复治疗效果。这些发现为未来卵巢癌新治疗策略的开发提供了重要的分子靶点和理论基础。
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