FGF2 promotes the chemotherapy resistance in colon cancer cells through activating PI3K/Akt signaling pathway

Abstract

To investigate the role of fibroblast growth factor 2 (FGF2) in chemotherapy resistance of colon cancer. An HCT116/5-fluorouracil (5-FU)–resistant cell line was established, and FGF2 levels were detected in a sensitive cell group (HCT116) and a resistant cell group (HCT1116-R) using different methods. Fibroblast growth factor 2 levels in the medium were determined by enzyme-linked immunoassay. The protein expressions of FGF2, fibroblast growth factor receptor 1 (FGFR1), and phospho-FGFR1 were assessed by Western blotting, and FGF2 mRNA levels were detected by quantitative real-time polymerase chain reaction. Fibroblast growth factor 2 recombinant protein was added to sensitive cells, and FGFR inhibitor AZD4547 was added to resistant cells, and the cell survival rate was determined using the cell counting kit-8 method and the protein expressions of PI3K (phosphatidylinositol 3 kinase), p-PI3K (phospho-PI3K), Akt (protein kinase B), p-Akt (phospho-Akt), mammalian target of rapamycin (mTOR), p-mTOR (phospho-mTOR), Bad (Bcl-xL/Bcl-2–associated death promoter), NF-κB (nuclear factor κB), GSK-3 (glycogen synthase kinase-3), FKHR (forkhead box protein O1), and PTEN (phosphatase and tensin homolog deleted on chromosome ten) were detected by Western blotting. Fibroblast growth factor 2 protein and mRNA expression levels in the HCT116-R group were significantly higher than those in the HCT116 group. Fibroblast growth factor 2 increased the survival rate of HCT116 cells; improved tolerance to 5-FU; upregulated p-PI3K, p-Akt, and p-mTOR; and downregulated Bad. The FGFR inhibitor AZD4547 decreased cell survival rate and tolerance to 5-FU; downregulated p-PI3K, p-Akt, and p-mTOR expression; and upregulated Bad. Fibroblast growth factor 2 promotes chemotherapy tolerance in colon cancer cells by activating the Akt/mTOR and Akt/Bad signaling pathways downstream of PI3K.