抗心律失常药E-4031对人胃癌细胞系SGC-7901的肿瘤生物学行为的调节作用  

Regulation Effects of Antiarrhythmic Drug E-4031 on Tumor Biologic Behavior of Gastric Cancer Cell Line SGC-7901

作　　者：吕清[1] 卢晓明[1] 舒晓刚[1] 孙仁虎[1] 崔静[2] 王国斌[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院胃肠外科,武汉430022 [2]华中科技大学同济医学院附属协和医院胰腺外科,武汉430022

出　　处：《医药导报》2010年第1期5-9,共5页Herald of Medicine

基　　金：国家自然科学基金资助项目(基金编号:30772128)

摘　　要：目的研究Ⅲ类抗心律失常药E-4031,即钾离子通道蛋白(HERG K+)特异性阻断药对胃癌细胞SGC-7901肿瘤生物学行为的调节作用,探讨其是否具有阻止胃癌发生、发展的功能。方法应用逆反应-聚合酶链反应(RT-PCR)及Western-blot方法检测胃癌细胞系SGC-7901中herg1基因的表达情况,并应用特异性钾离子通道蛋白阻断药Ⅲ类抗心律失常药E-4031阻断胃癌细胞HERG K+通道,研究E-4031对胃癌细胞生长、增殖、凋亡及侵袭能力等肿瘤生物学行为的调节作用。结果herg1基因在胃癌细胞系SGC-7901中呈现过度表达,当其表达HERG K+通道蛋白被Ⅲ类抗心律失常药E-4031阻断后,胃癌细胞增殖降低,G0/G1细胞增多,凋亡增加(P<0.01),并且其侵袭转移能力降低。结论HERG K+通道蛋白在胃癌中表达过度,而其特异性阻断药E-4031具有调节胃癌细胞肿瘤生物学行为和抑制肿瘤细胞生长增殖的功能。Objective To investigate the regulation effects of the class III antiarrhythmic drug E-4031, HERG K^＋ channels specific blocker on hergl gene expressed in gastric carcinoma cell line SGC-7901, and explore whether it could prevent tmnorigenesis of gastric carcinoma. Methods Reverse Transcription PCR assay and western-blot analysis were used to detect the expression of hergl gene on cell line SGC-7901. By blocking the channels with the class III antiarrhythmic drug E-4031, the tumor cell invasion, proliferation and apoptosis were analyzed. Results The hergl gene was over expressed in the gastric cancer cells. While, the cell population at GO/G1 phase and apoptotic number of tumor cells were increased（ P 〈 0.01 ）, and less tumor cell proliferated was found when HERG K^＋ channel was blocked by E-4031 （ P 〈 0. 05 ）. Moreover, the drug inhibited cell migration （ P 〈 0.05 ）. Conclusion HERG K^＋ channels were probably overexpressed in the gastric cancer cell line SGC- 7901 and the class III antiarrhythmic drug E-4031 could make a important role in regulating the biological behavior of tumor cells and suppressing the growth of tumor.

关 键 词：E-4031 抗心律失常药 HERG K+通道蛋白 胃癌 增殖 凋亡 侵袭 

分 类 号：R972.2[医药卫生—药品] R735.2[医药卫生—药学]