山西医科大学学报2026,Vol.57Issue(4):361-367,7.DOI:10.13753/j.issn.1007-6611.2026.04.001
敲低RASSF9通过抑制PI3K/AKT通路提高耐药肺腺癌细胞对阿美替尼的敏感性
RASSF9 knockdown enhances sensitivity of drug-resistant lung adenocarcinoma cells to Almonertinib by inhibiting the PI3K/AKT pathway
摘要
Abstract
Objective To investigate the effect of Ras association domain family member 9(RASSF9)on Almonertinib resistance in lung adenocarcinoma cells and clarify its molecular mechanism.Methods RASSF9 interference lentivirus and its corresponding negative control(NC)vector were constructed and transfected into Almonertinib-resistant cell lines HCC827/AR and H1975/AR,respectively.The cells were divided into control group,NC group and shRASSF9 group.The concentration gradient escalation method was used to determine the half-maximal inhibitory concentration(IC₅₀)of Almonertinib in drug-resistant cells after RASSF9 knock-down.The proliferation and apoptosis of drug-resistant cells were detected by CCK-8 assay and flow cytometry,respectively.The expressions of RASSF9 and PI3K/Akt pathway-related proteins were detected by Western blot.Results Compared with control group and NC group,the IC₅₀ values of Almonertinib to HCC827/AR and H1975/AR cells significantly decreased in shRASSF9 group(P<0.01).Compared with control group and NC group,the viabilities of drug-resistant cells significantly decreased,while the cell apoptosis rate significantly increased in shRASSF9 group(all P<0.01).Western blot analysis showed that the expression of RASSF9 and the ratios of p-PI3K/PI3K and p-AKT/AKT in HCC827/AR and H1975/AR cells in shRASSF9 group were significantly decreased compared with control group and NC group(P<0.01).Conclusion RASSF9 knockdown can reduce the resistance of lung adenocarcinoma drug-resistant cells to Almonertinib,which is associated with the inhibition of PI3K/Akt signaling pathway.关键词
阿美替尼/耐药/肺腺癌/RASSF9/PI3K/Akt通路Key words
Almonertinib/drug resistance/lung adenocarcinoma/RASSF9/PI3K/Akt signaling pathway分类
医药卫生引用本文复制引用
洪海宁,李芷依,张静,刘军,张松,张炳太,黄庭,王安生..敲低RASSF9通过抑制PI3K/AKT通路提高耐药肺腺癌细胞对阿美替尼的敏感性[J].山西医科大学学报,2026,57(4):361-367,7.基金项目
蚌埠医科大学科技项目自然科学类重点项目(2023byzd119) (2023byzd119)