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Abstract
Introduction Ovarian clear cell carcinoma (OCCC) is relatively resistant to platinum-based chemotherapy, which is associated with a poor prognosis. Evidence is mounting that fibroblast growth factors (FGFs) play key roles in human malignancies. However, the impact of FGF11 on OCCC is not completely understood.
Methods Twenty-four patients who were diagnosed with OCCC in FIGO stage II-IV were included. According to their response to first-line platinum-based chemotherapy, patients were classified into two groups: the chemoresistant (CR) group and the chemosensitive (CS) group. Nanostring nCounter PanCancer Pathway panel was performed to explore expression profiles in OCCC showing different chemosensitivity. shRNA targeting FGF11 was utilized to knock down the expression of FGF11 in OCCC cell lines. Colony formation assay, CCK-8 assay, wound healing, transwell invasion assay and flow cytometric analysis were subsequently performed to detect the effect of FGF11 on OCCC cell progression and cisplatin (DDP) chemoresistance. Western blot assays and rescue experiments were employed to examine the mechanism of FGF11 in OCCC.
Results Expression and bioinformatic analysis verified that FGF11 was significantly upregulated in chemoresistant OCCC tissues and higher expression of FGF11 was related to poorer survival. Downregulation of FGF11 inhibited cancer progression and DDP chemoresistance of OCCC cells. Mechanistically, FGF11 was regulated by the HIF-1α/FGF11 signaling axis. Inhibition of cancer cell progression and DDP chemoresistance caused by HIF-1α knockdown can be rescued by the overexpression of FGF11.
Conclusion/Implications FGF11 promoted cancer progression and DDP chemoresistance via the HIF-1α/FGF11 signaling axis in OCCC, suggesting the potential of HIF-1α/FGF11 signaling axis as a therapeutic target for OCCC.
