Open AccessFGF9 promotes cisplatin resistance in colorectal cancer via regulation of Wnt/β‑catenin signaling pathway
Author(s) -
Zhijin Zhang,
Yuhao Zhang,
Xinju Qin,
Yuexia Wang,
Jun Fu
Publication year - 2019
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2019.8399
Subject(s) - wnt signaling pathway , cisplatin , cancer research , gene silencing , colorectal cancer , cell cycle , signal transduction , apoptosis , adenomatous polyposis coli , biology , cancer , medicine , microbiology and biotechnology , chemotherapy , biochemistry , gene
Development of cisplatin resistance in colorectal cancer is largely caused by dysregulation of signaling pathways, including the Wnt/β-catenin signaling pathway, in cancer cells. Further investigation into the molecular mechanism of chemoresistance could improve outcomes for patients with colorectal cancer. The present study determined that fibroblast growth factor 9 (FGF9) was overexpressed in tumor tissues compared with normal tissues from patients with colorectal cancer. Using the colorectal cancer cell line LoVo, transfection of recombinant FGF9 decreased cisplatin-induced cell apoptosis whilst FGF9 silencing increased cisplatin-induced apoptosis. Western blot analysis and reverse transcription-quantitative polymerase chain reaction demonstrated that FGF9 decreased adenomatous polyposis coli (APC) mRNA and protein expression and contributed to activation of the Wnt/β-catenin signaling pathway. Notably, an increase in FGF9 and β-catenin protein expression and a decrease in APC protein expression was observed in the established LoVo cisplatin resistant cell line (LoVo/cisplatin). Silencing of FGF9 reversed cisplatin resistance of LoVo/cisplatin cells. In conclusion, the present findings suggested that FGF9 activated the Wnt signaling pathway and was a mediator of cisplatin resistance in colorectal cancer.