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FGF9 promotes cisplatin resistance in colorectal cancer via regulation of Wnt/β-catenin signaling pathway
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026987/ https://www.ncbi.nlm.nih.gov/pubmed/32104224 http://dx.doi.org/10.3892/etm.2019.8399 |
Sumario: | 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. |
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