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  

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

作　　者：王凤玲[1] 杨育才[2] 李谦[1] 王立强[1] 

机构地区：[1]华侨大学生物医学学院,福建泉州362021 [2]台湾大学生化科学系,台湾台北106170

出　　处：《华侨大学学报（自然科学版）》2015年第5期552-557,共6页Journal of Huaqiao University(Natural Science)

基　　金：福建省自然科学基金资助项目(2010J01208);福建省泉州市科技计划重点项目(2013Z35)

摘　　要：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72h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-Ras突变导致的吉非替尼原发耐药型A549细胞具有较好的体外抗肿瘤活性,其机制与抑制EGFR及PI3K/AKT/mTOR信号通路的活化有关.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.TW918could 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.

关 键 词：K-RAS突变 肺腺癌 吉非替尼 表皮生长因子受体 PI3K/AKT/MTOR 信号通路 

分 类 号：R963[医药卫生—微生物与生化药学]