Aumolertinib combined with anlotinib inhibits proliferation of non-small cell lung cancer cells by down-regulating the PI3K/AKT pathway
10.12122/j.issn.1673-4254.2024.10.15
- VernacularTitle:阿美替尼联合安罗替尼通过下调PI3K/AKT通路抑制非小细胞肺癌细胞的增殖
- Author:
Yumei YANG
1
;
Xuerou LIU
;
Wei LIU
;
Xingqi ZHOU
;
Zhen ZHANG
;
Yan HU
;
Peipei LIU
;
Xian LI
;
Hao LIU
;
Shanshan LI
Author Information
1. 蚌埠医科大学药学院,安徽省生化药物工程技术研究中心,安徽 蚌埠 233030
- Keywords:
non-small cell lung cancer;
aumolertinib;
anlotinib;
apoptosis;
invasion and migration;
PI3K-Akt pathway
- From:
Journal of Southern Medical University
2024;44(10):1965-1975
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of aumolertinib combined with anlotinib on proliferation of non-small cell lung cancer(NSCLC)cells.Methods CCK-8 assay,colony formation assay,and flow cytometry were used to assess the effect of different concentrations of aumolertinib or anlotinib on proliferation,survival,and apoptosis of PC-9 and HCC827 cells,and their synergistic effect was evaluated using the SynergyFinder model.In PC-9 and HCC827 cells treated with aumolertinib combined with anlotinib,the changes in cell invasion and migration abilities were assessed with Transwell assay,and the expressions of apoptosis-and invasion/migration-related proteins(Bax,Bcl-2,E-cadherin,vimentin,MMP2,and MMP9)and the key PI3K-Akt pathway proteins were detected using Western blotting.Results In PC-9 cells,the IC50 of aumolertinib and anlotinib was 1.701 μmol/L and 4.979 μmol/L,respectively,with a synergy score(ZIP)of 19.112;in HCC827 cells,their IC50 was 2.961 μmol/L and 7.934 μmol/L,respectively,with a ZIP of 12.325.Compared with aumolertinib and anlotinib used alone,their combined treatment more strongly inhibited the proliferation and survival,enhanced apoptosis and suppressed invasion and migration abilities of PC-9 and HCC827 cells.Western blotting showed that in both PC-9 and HCC827 cells,the combined treatment significantly upregulated the expressions of E-cadherin and Bax proteins,downregulated the expressions of Bcl-2,vimentin,MMP2,and MMP9 proteins,and reduced phosphorylation levels of PI3K and Akt.Conclusion Aumolertinib combined with anlotinib can effectively inhibit NSCLC cell proliferation by downregulating the PI3K-Akt pathway,suggesting a potentially new option for NSCLC treatment.
