中国药理学通报2026，Vol.42Issue(2)：304-311,8.DOI:10.12360/CPB202502033
AurkC调控DNA损伤修复蛋白表达对非小细胞肺癌吉非替尼获得性耐药的机制
AurkC regulates the expression of DNA damage repair proteins and affects the acquired resistance to gefitinib in non-small cell lung cancer
摘要
Abstract
Aim To study the mechanism of AurkC resistance to gefitinib in non-small cell lung cancer cells.Methods Human lung cancer HCC827 and ge-fitinib resistant HCC827GR cells were cultured in vitro,cell proliferation was detected by MTT assay,and AurkC protein expression was detected in the drug-resistant cell model.AurkC overexpression cell line was constructed,and the protein expression level of γ-H2AX(S139)in the nucleus and DNA damage foci in nucleus were detected by Western blot and immuno-fluorescence staining.The degree of DNA damage was assessed by comet assay,and the expression of pro-teins related to DNA damage repair was detected by Western blot.Results The IC50 of HCC827 and the IC50 of HCC827GR were 0.004±0.001 μmol·L-1 and the IC50 of HCC827GR was 14.630±5.348 μmol·L-1 and the drug resistance index was 3 402.326,indicat-ing that HCC827GR was highly tolerant to gefitinib.Western blot results showed that the expression level of AurkC in drug-resistant cell lines was much higher(P<0.01)than that in sensitive cell lines.Compared with the negative control group,the expression level of γ-H2AX protein in the overexpression group was sig-nificantly reduced(P<0.01)after gefitinib stimula-tion,the DNA damage foci in the nucleus significantly decreased(P<0.01),and the olive tail distance in the cells significantly decreased(P<0.01).The expres-sion levels of DNA damage repair function related mol-ecules TP53BP1,ATR,p-ATR,ATM,p-ATM and MRE11,BRCA1 and p-BRCA1 were significantly down-regulated(P<0.01).Conclusion AurkC pro-motes gefitinib resistance in non-small cell lung cancer by inhibiting the expression of DNA damage repair re-lated proteins.关键词
非小细胞肺癌/吉非替尼/耐药机制/AurkC/γ-H2AX/DNA损伤修复Key words
NSCLC/gefitinib/drug resistance mechanism/AurkC/γ-H2AX/DNA damage repair分类
医药卫生引用本文复制引用
莫建梅,黄少远,朱峰..AurkC调控DNA损伤修复蛋白表达对非小细胞肺癌吉非替尼获得性耐药的机制[J].中国药理学通报,2026,42(2):304-311,8.基金项目
广西高校中青年教师(科研)基础能力提升项目(No 2022KY0478) （科研）
桂林医学院大学生创新创业训练计划国家级项目(No 202310601007) （No 202310601007）
广西壮族自治区卫健委西医类别自筹经费科研课题(No Z-C20250801) （No Z-C20250801）
