成纤维细胞生长因子11（FGF11）通过缺氧诱导因子-1α/HIF-1α信号轴促进卵巢透明细胞癌的进展和顺铂耐药。

Fibroblast Growth Factor 11 (FGF11) Promotes Progression and Cisplatin Resistance Through the HIF-1α/FGF11 Signaling Axis in Ovarian Clear Cell Carcinoma.

作者信息

Yin Min, Lu Chunli, Zhou Huimei, Liu Qian, Yang Jiaxin

机构信息

National Clinical Research Center for Obstetric and Gynecologic Diseases, Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Neurospine Center, China International Neuroscience Institute (CHINA-INI), Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, People's Republic of China.

出版信息

Cancer Manag Res. 2023 Jul 26;15:753-763. doi: 10.2147/CMAR.S414703. eCollection 2023.

DOI:10.2147/CMAR.S414703

PMID:37525667

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10387280/

Abstract

BACKGROUND

A poor prognosis is often associated with ovarian clear cell carcinoma (OCCC) due to its relative resistance to platinum-based chemotherapy. Although several studies have been launched to explore the pathogenesis of OCCC, the mechanism of chemoresistance has yet to be uncovered.

METHODS

Nanostring nCounter PanCancer Pathways Panel was performed to explore the expression profiles of OCCC tissues from patients showing different platinum sensitivity. Bioinformatic analysis was performed to select genes associated with chemoresistance and cell function assays, including colony formation, wound healing, transwell and flow cytometric analysis, were used to explore the role of the target gene in the progression of OCCC and resistance to cisplatin (DDP).

RESULTS

Gene expression profiles and bioinformatic analysis verified that the expression of fibroblast growth factor 11 (FGF11) was significantly increased in platinum-resistant OCCC tissues and increased FGF11 expression was related to poorer survival. Downregulation of FGF11 inhibited the proliferation, migration, and invasion, reversing the DDP resistance of OCCC cells. Mechanically, FGF11 was regulated by hypoxia-inducible factor-1α (HIF-1α) to modulate the DDP sensitivity.

CONCLUSION

FGF11 was highly expressed in platinum-resistant OCCC tissues, promoting progression and resistance to DDP through the HIF-1α/FGF11 signaling axis.

摘要

背景

卵巢透明细胞癌（OCCC）通常预后较差，因为其对铂类化疗相对耐药。尽管已经开展了多项研究来探索OCCC的发病机制，但化疗耐药机制仍未明确。

方法

采用纳米String nCounter泛癌通路分析试剂盒检测不同铂敏感性患者的OCCC组织的表达谱。进行生物信息学分析以选择与化疗耐药相关的基因，并采用包括集落形成、伤口愈合、Transwell和流式细胞术分析在内的细胞功能试验，来探究目标基因在OCCC进展和顺铂（DDP）耐药中的作用。

结果

基因表达谱和生物信息学分析证实，成纤维细胞生长因子11（FGF11）在铂耐药OCCC组织中的表达显著增加，且FGF11表达增加与较差的生存率相关。FGF11的下调抑制了细胞增殖、迁移和侵袭，逆转了OCCC细胞对DDP的耐药性。机制上，FGF11受缺氧诱导因子-1α（HIF-1α）调控，从而调节DDP敏感性。