Objective To investigate the effects of fibroblast growth factor receptor 1 (FGFR1) on the resistance of colorectal cancer (CRC) cells to oxaliplatin (OXA).

Methods An OXA-resistant cell line (HCT8/OXA) was established by treating HCT8 CRC cells with low-dose OXA for a long period in vitro. The CCK-8 assay was used to compare the viability of the HCT8 and HCT8/OXA cells after OXA treatment and to examine their resistance to the anticancer drug. Second-generation high-throughput sequencing technology was used to identify differentially expressed genes between the parental and drug-resistant cells. The expression of FGFR1 in the HCT8 and HCT8/OXA cells was detected by Western blot assay. Colony formation and flow cytometric assays were used to determine cell proliferation and apoptosis, respectively. The expression of PI3K/AKT signaling pathway-related proteins was detected using Western blot assay.

Results Compared with the levels in the HCT8 cells, the FGFR1 levels were significantly increased in the HCT8/OXA cells (P<0.01). FGFR1 overexpression in the HCT8 cells increased their drug resistance (P<0.01) and proliferation (NC+OXA: 236.67±6.24; FGFR1+OXA: 568.33±6.24) and decreased their apoptotic rate after OXA treatment (NC+OXA: 27.83±0.85; FGFR1+OXA: 17.47±1.25). FGFR1 knockdown in the HCT8/OXA cells reduced their drug resistance (P<0.01) and proliferative ability (Si-NC+OXA: 411±8.29; Si-FGFR1+OXA: 233.33±20.55) and increased their apoptotic rate (Si-NC+OXA: 2.85±0.17; Si-FGFR1+OXA: 14.42±0.77). FGFR1 inhibited the activity of the PI3K/AKT signaling pathway and cell apoptosis and improved the proliferation and drug resistance of the CRC cells. By contrast, an activator of the PI3K/AKT pathway blocked the effects of FGFR1 on this signaling pathway and drug resistance in the CRC cells.

Conclusions FGFR1 can inhibit the PI3K/AKT signaling pathway and thereby reduce the sensitivity of CRC cells to OXA.