Construction of apatinib-resistant cell lines in hepatocellular carcinoma and study of resistant genes
BO Lun
WANG Xiangxu
JI Hongchen
AI Liping
BAI Yinmiao
LIU Yang
ZHANG Hongmei
Abstract：Objective To explore the potential resistance mechanism of hepatocellular carcinoma cells to apatinib.Methods Human SNU-739/SNU-878 hepatocellular carcinoma cell lines were selected to construct apatinib-resistant cell lines.Antimicrobial susceptibility testing was carried out on parental and drug-resistant cells by cell viability detection and plate clone formation assay,the gene expression profiles of parental and drug-resistant cells were detected by RNA chip technology,and the key genes mediating apatinib resistance were screened out according to the expression differences.qRT-PCR and Western blotting were used to verify the key genes,and the effect of stable overexpression of key genes on cell drug resistance was detected by antimicrobial susceptibility testing.Results The cell viability and number of clones formed in apatinib-resistant cell lines were significantly higher than those in parental cells(P＜0.05).A key gene,carbamoyl phosphate synthetase 1(CPS1),was screened out,and its mRNA and protein levels were significantly down-regulated in drug-resistant cell lines(P＜0.05).Overexpression of CPS1 significantly reduced the viability and clonal formation ability of hepatocellular carcinoma cells(P＜0.05).Conclusion CPS1 may be a key gene that mediates apatinib resistance in hepatocellular carcinoma cells.
Keywords：hepatocellular carcinomaapatinibdrug resistancecarbamoyl phosphate synthetase 1
Publication Date：2024-07-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：6( 763-768 )