人工合成钠离子通道阻断剂抑制前列腺癌细胞的生长及侵袭  

Artificial sodium channel amine ligands suppress growth and invasion in prostate cancer cells in vitro

作　　者：周蕊[1,2] 卢宗亮[1,2] 刘凯[2] 杨柳娜[1] 胡叶敏[3] 常徽[2] 周永[2] 糜漫天[2] 李雁武[3] 许红霞[1,2] 

机构地区：[1]第三军医大学大坪医院野战外科研究所营养科,重庆400042 [2]第三军医大学军事预防医学院营养与食品卫生学教研室,重庆市营养与食品安全重点实验室,重庆市医学营养研究中心,重庆400038 [3]重庆医科大学药学院,重庆400016

出　　处：《第三军医大学学报》2014年第5期422-426,共5页Journal of Third Military Medical University

基　　金：重庆市自然科学基金(2011BB5027);重庆市留学人员科技活动项目(2011)~~

摘　　要：目的研究人工合成钠离子通道阻断剂(sodium channel amine ligands,SCALs)对前列腺癌细胞株(PC3细胞、DU145细胞)生长及侵袭的影响,以筛选高效的抗肿瘤药物。方法四甲基偶唑氮(MTT)法检测SCALs对肿瘤细胞的存活率的影响;Transwell侵袭实验检测SCALs干预后肿瘤细胞体外侵袭能力的变化;流式细胞仪检测SCALs促进细胞凋亡及阻滞细胞周期的能力,蛋白免疫印迹实验检测SCALs对钠离子通道蛋白α亚基Nav 1.7蛋白表达的影响。结果7种SCALs中的3种(S1127、S1169、S1180)对前列腺癌细胞敏感,在低浓度时对肿瘤细胞具有杀伤效应,且其抑制率与药物浓度呈剂量-效应关系,其中S1180对PC3和DU145细胞的IC50分别为2.9μmol/L和2.5μmol/L,在10μmol/L时能促进12.89%的肿瘤细胞凋亡、抑制75.53%的细胞侵袭,并具有阻滞细胞周期的能力,以及能下调Nav 1.7蛋白的表达水平。结论合成的钠离子通道阻断剂中3种SCALs尤其是S1180具有显著杀伤前列腺癌细胞效应,将来可能成为治疗肿瘤的一类新型药物。Objective To determine the effect of artificially synthesized ligands （SCALs） on the growth and invasion of prostate cancer cell lines. Methods sodium channel amine SCALs compounds, Sl127, Sl156, Sl169, $1170, Sl178, Sl180, and Sl182 were synthesized and confirmed. Prostate cancer cell lines, PC3 and DU145, were used in this study. The cell viability was assessed by Mql＇ assay in the cells after the treatment of SCALs respectively. The cell apoptosis and cell cycle progression were assessed by flow cytometry. The cancer cell invasion was assessed by Transwell chamber assay. The protein expression of prostate cancer sodium channel c~ subunit, Nav 1.7 was determined by Western blotting. FlesulIs Three compounds, Sl127, Sl169, and Sl180, inhibited the growth of tumor cells in a dose-dependent manner. Sl180 was found to be the most potent among the 7 compounds. The IC50 values of Sl180 were 2.9 and 2.5 lxmol/L respectively for PC3 and DU145 ceils. At 10 txmol/L, Sl180 improved cell apoptosis in 12.89% PC3 cells, and suppressed the cell invasion in 75.53% cells, and exerted significant effects on cell arrest, and down-regulated Nay 1.7 protein expression. Conclusion Three SCALs compounds, especially Sl180, have obvious anti-tumor effect on prostate cancer cells, and might be a potential therapeutic agent for prostate cancer.

关 键 词：电压门控性钠离子通道 钠离子通道胺类配体 前列腺癌 PC3细胞 肿瘤侵袭 

分 类 号：R329.21[医药卫生—人体解剖和组织胚胎学] R737.25[医药卫生—基础医学]