FGFR1 reduces the sensitivity of colorectal cancer cells to oxaliplatin by inhibiting the activity of PI3K/AKT signaling pathway
10.12354/j.issn.1000-8179.2025.20250141
- VernacularTitle:FGFR1通过调控PI3K/AKT通路抑制结直肠癌对奥沙利铂的药物敏感性
- Author:
Cao LUYANG
1
;
Zuo HAOJIAN
;
Chen HAN
;
Peng XIAOMEI
;
Shi XINPENG
;
Luo XIAOYONG
Author Information
1. 洛阳市中心医院,洛阳市恶性肿瘤个体化诊断及治疗重点实验室(河南省 洛阳市 471000)
- Publication Type:Journal Article
- Keywords:
colorectal cancer(CRC);
fibroblast growth factor receptor 1(FGFR1);
PI3K/AKT signaling pathway;
oxaliplatin(OXA)
- From:
Chinese Journal of Clinical Oncology
2025;52(8):379-385
- CountryChina
- Language:Chinese
-
Abstract:
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 exam-ine their resistance to the anticancer drug.Second-generation high-throughput sequencing technology was used to identify differentially ex-pressed 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 sig-naling 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.
