TRIM24介导肺癌细胞吉非替尼耐药机制探讨  

Mechanism of TRIM24 to Regulate Resistance of Gefitinib in NSCLC cells

作　　者：李海英[1] 王庆苓[1] 包海军[1] 张恒[1] 庄莹[1] 

机构地区：[1]徐州医学院基础医学院病理教研室,徐州221000

出　　处：《中国肺癌杂志》2016年第1期24-29,共6页Chinese Journal of Lung Cancer

基　　金：国家自然科学基金项目(No.81101493);国家自然科学基金项目(No.81302612);徐州医学院人才项目启动基金(No.D2014003)资助~~

摘　　要：背景与目的表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI)的原发和继发性耐药已成为其在临床肺癌治疗中的拦路虎,在肺癌组织中研究发现TRIM24呈高表达状态,在肺癌细胞中能调控细胞增殖、周期和细胞凋亡,本研究旨在进一步探讨TRIM24调控肺癌细胞吉非替尼耐药的分子机制。方法应用MTT方法和流式细胞仪检测干扰TRIM24及干扰TRIM24后加入吉非替尼对肺癌细胞系增殖能力及凋亡率的抑制率的变化,同时应用Western blot方法检测凋亡相关基因的变化及AKT信号通路中蛋白的表达。结果在A549细胞中使用干扰TRIM24可以提高吉非替尼对肿瘤增殖能力的抑制率,增加吉非替尼诱导的凋亡水平,同时干扰TRIM24及干扰TRIM24加入吉非替尼后促凋亡相关基因p-BAD、Bcl-2和AKT及AKT信号通路相关蛋白PIK3CA均出现降低。结论 TRIM24能够调控肺癌细胞吉非替尼耐药,并且通过AKT信号通路引起肺癌细胞EGFRTKI耐药。Background and objective Epidermal growth factor receptor tyrosine kinase inhibitor（EGFR-TKI） resistance significantly limits its use in clinical practice. Study found that TRIM24 was overexpressed in non-small cell lung cancer（NSCLC） tissues and regulate cell growth, cell cycle and apoptosis in lung cell lines. The aim of this study is to explore the mechanism of TRIM24 to regulate resistance of Gefitinib in NSCLC cells. Methods MTT and apoptosis were used to detect the change of cell grow and cell apoptosis with down-expression TRIM24 and Sh TRIM24 with presence of Gefitinib. Meanwhile, Western blot was used to detect the expression of protein related to apoptosis and AKT signal path. Results TRIM24 interference could improve the effect of gefitinib on cell growth inhibition and upregulate the cell apoptosis in A549 cell. Down-regulated of endogenous TRIM24 and Sh TRIM24 with Gifitinib could also reduce the protein related apoptosis, such as p-BAD and Bcl-2, and the protein PIK3 CA related AKT signal path in A549 cell. Conclusion TRIM24 could regulate required resistance to Gefitinib via Akt pathway in NSCLC.

关 键 词：肺肿瘤 吉非替尼 表皮生长因子受体酪氨酸激酶抑制剂 

分 类 号：R734.2[医药卫生—肿瘤]