Study on effects of high expression of IGF2BP1 on paclitaxel-resistant ovarian cancer cells and its mechanisms
YU Yue
CHEN Xiaoying
LIU Xia
YIN Fuqiang
Abstract：Objective To explore the effects of high expression of insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)on paclitaxel-resistant ovarian cancer cells and its mechanisms.Methods Kaplan-Meier Plotter database and ROC Plotter database were used to analyze the correlations of IGF2BP1 expression with the ovarian cancer patients'prognosis and paclitaxel resistance,respectively.The ovarian cancer cell line SKOV3 sensitive to paclitaxel and the ovarian cancer cell line SKOV3-R resistant to paclitaxel were selected for experiment.IGF2BP1-overexpressing lentivirus and empty vector were transfected into SKOV3-R cells,which were named S-R-IGF2BP1-OE cells and S-R-EV cells,respectively.Cell proliferation activity was detected by using CCK-8 assay.The expression of IGF2BP1 mRNA was detected by using reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR).Cell cycle distribution was detected by using flow cytometry.The expression levels of cell cycle-related factors were detected by using Western blot assay.Results High expression of IGF2BP1 was significantly correlated with worse overall survival(OS)and progression-free survival(PFS)in the ovarian cancer patients(P＜0.05).The expression level of IGF2BP1 mRNA in the chemotherapy-resistant group was significantly higher than that in the chemotherapy-sensitive group(P＜0.05).The expression level of IGF2BP1 mRNA in SKOV3-R cells was significantly higher than that in SKOV3 cells(P＜0.05).Under the intervention of paclitaxel,the proliferation activity of S-R-IGF2BP1-OE cells was higher than that of S-R-EV cells(P＜0.05).The half maximal inhibitory concentration(IC50)of paclitaxel for S-R-IGF2BP1-OE cells and the IC50 of paclitaxel for S-R-EV cells were 187.02 nmol/L and 98.76 nmol/L,respectively.The proportions of G0/G1 phase and G2/M phase in S-R-IGF2BP1-OE cells were significantly lower than those in S-R-EV cells(P＜0.05).The expression level of cyclin A2 in S-R-IGF2BP1-OE cells was higher than that in S-R-EV cells,and the expression levels of p27 kinase inhibitor protein 1(p27 KIP1),p27 CDK-interacting protein 1(p21 Cip1),glycogen synthase kinase-3β(GSK-3 β),and cell cyclin-dependent kinase 7(CDK7)in S-R-IGF2BP1-OE cells were lower than those in S-R-EV cells,and the differences were statistically significant(P＜0.05).Conclusion High expression of IGF2BP1 is associated with poor prognosis in ovarian cancer patients,which may mediate paclitaxel resistance by regulating the cell cycle of ovarian cancer cells.
Keywords：Insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)Ovarian cancerPaclitaxelDrug resistanceCell cycle
Publication Date：2025-11-30
Online Publishing Date：2025-12-25(First online date of this platform, not the publication date of the document)
Pages：7( 1241-1247 )