苯丁酸钠联合吉非替尼对肺腺癌A549细胞增殖、迁移的影响及机制  

Effects of sodium phenylbutyrate combined with gefitinib on proliferation and migration of lung adenocarcinoma A549 cells

作　　者：张振安[1] 张静[1] 张风林[1] 袁亚军[1] 

机构地区：[1]唐山市人民医院,河北唐山063000

出　　处：《山东医药》2015年第38期14-17,共4页Shandong Medical Journal

基　　金：河北省自然科学基金资助项目(20101112)

摘　　要：目的研究苯丁酸钠联合吉非替尼对肺腺癌A549细胞增殖、迁移的影响,并探讨其机制。方法将体外培养的肺腺癌A549细胞分为空白对照组、吉非替尼组、苯丁酸钠组、联合处理组,各组均加入不含FBS的DMEM培养基,另外吉非替尼组加1 mmol/L吉非替尼,苯丁酸钠组加5μmol/L苯丁酸钠,联合处理组加1 mmol/L吉非替尼和5μmol/L苯丁酸钠。培养24 h后,用MTT法检测各组细胞OD450值,用流式细胞术检测各组细胞周期分布,用RT-PCR法检测凋亡相关基因survivin、BRAF、Notch1、MMP1、MMP2、MMP3、MMP9 mRNA,行划痕实验检测细胞迁移能力。结果与空白对照组相比,联合处理组、苯丁酸钠组、吉非替尼组OD450值、S期细胞比例、细胞迁移率及凋亡相关分子survivin、BRAF、Notch1、MMP1、MMP2、MMP3、MMP9 mRNA降低,G0/G1期细胞比例升高,P均<0.05。与苯丁酸钠组、吉非替尼组相比,联合处理组OD450值、S期细胞比例、细胞迁移率及凋亡相关分子survivin、BRAF、Notch1、MMP1、MMP2、MMP3、MMP9 mRNA降低,G0/G1期细胞比例升高,P均<0.05。结论苯丁酸钠和吉非替尼均能抑制肺腺癌细胞的增殖和迁移过程,其机制可能与降低细胞survivin、BRAF、Notch1、MMP1、MMP2、MMP3、MMP9 mRNA表达有关,两种药物联合应用具有协同作用。Objective To study the effects of sodium phenylbutyrate combined with gefitinib on proliferation and migration of lung adenocarcinoma A549 cells and to investigate the mechanism. Methods The lung adenocarcinoma A549 cells were cultured and divided into the blank control group（ treated with DMEM medium without FBS）,gefitinib group（ treated with 1 mmol/L gefitinib）,sodium phenylbutyrate group（ treated with 5 μmol/L sodium phenylbutyrate） and the combined treatment group（ treated with 1 mmol / L gefitinib and 5 mol / L sodium phenylbutyrate）. After culture for 24 h,the OD450 was detected by MTT method and the cell cycle distribution was detected by flow cytometry. The expression of apoptosis-related genes survivin,BRAF,Notch1,MMP-1,MMP-2,MMP-3 and MMP-9 was detected by RT-PCR. The cell migration was assayed by scratch test. Results Compared with the blank control group,the OD450,cell proportion in S phase,cell mobility and the expression of survivin,BRAF,Notch1,MMP-1,MMP-2,MMP-3 and MMP-9 mRNA were decreased,and the cell proportion in G0 / G1 phase was increased in the combined treatment group,sodium phenylbutyrate group and gefitinib group（ all P〈0. 05）. Compared with the sodium phenylbutyrate group and gefitinib group,the OD450,cell proportion in S phase,cell mobility and the expression of survivin,BRAF,Notch1,MMP-1,MMP-2,MMP-3 and MMP-9 mRNA were decreased,and the cell proportion in G0 / G1 phase was increased in the combined treatment group（ all P〈0. 05）. Conclusion The sodium phenylbutyrate and gefitinib can both inhibit the proliferation and migration process of lung adenocarcinoma,which may be related with the decreased expression of survivin,BRAF,Notch1,MMP-1,MMP-2,MMP-3 and MMP9 mRNA. The combined application of the two drugs has synergistic effect.

关 键 词：肺腺癌 苯丁酸钠 吉非替尼 细胞增殖 细胞周期 细胞迁移 细胞凋亡 凋亡相关基因 

分 类 号：R734.2[医药卫生—肿瘤]