候选药物TW918对K-Ras突变型人肺腺癌A549细胞的体外抑制作用

探讨候选药物TW918对K-Ras突变型人肺腺癌A549细胞的体外抑制作用.以MTT法检测TW918对A549细胞的增殖抑制作用;流式细胞术检测A549细胞周期和凋亡的变化;Western blotting 检测相关蛋白的表达.结果表明:候选药物TW918可以以时间和剂量依赖性地抑制A549细胞的增殖,且作用72 h时抑制效果比吉非替尼高9.93倍;引起细胞周期阻滞于G1期,并诱导细胞发生凋亡;降低A549细胞中p-EGFR的表达,并抑制其下游PI3K/AKT/mTOR信号通路的激活.TW918对K-Ra

In Vitro Inhibition Effects a Candidate Drug TW918 on K-Ras Mutatant Human Lung Adenocarcinoma Cell Line A549

This paper is to report the study of the in vitro inhibition effects of a candidate drug TW918 on human lung adenocarcinoma cell line A549, which is heterozygous for the K-Ras mutations. Antiproliferative effects on A549 cells was assessed by MTT assay. Cell cycle distribution and apoptosis were detected by flow cytometer. The protein expression was measured by Western blotting. TW918 showed a strong inhibition of A549 cells proliferation in a time and concentration dependent manner, 9.93 times higher than gefitinib after 72 h. TW918 could induce cell cycle arrested at G1 phase and apoptosis. TW918 also inhibited the expression of p-EGFR and the activation of PI3K/AKT/mTOR signal pathway in A549 cells. In conclusion, TW918 has the antitumor effects on gefitinib resistant cell line A549, bearing the K-Ras mutations, through inhibiting EGFR and PI3K/AKT/mTOR signal pathway.