异丙酚对人胃癌细胞RhoA/ROCK1信号通路的影响  

Effect of propofol on RhoA/ROCK1 signaling pathway in human gastric cancer cells

作　　者：赖晓红[1] 梁桦[1] 杨承祥[1] 刘洪珍[1] 

机构地区：[1]佛山市第一人民医院麻醉科,528000

出　　处：《中华麻醉学杂志》2015年第4期434-437,共4页Chinese Journal of Anesthesiology

基　　金：佛山市卫生局医学科研课题立项（2014024）

摘　　要：目的 初步评价Ras同源基因（Rho）/Rho相关螺旋卷曲蛋白激酶（ROCK）信号通路在异丙酚抑制人胃癌细胞转移能力中的作用.方法 体外培养人胃癌MKN-45细胞浓度为1.0× 106个/ml,接种培养板后按照随机数字表法,将细胞培养板孔分为4组：C组不给予任何药物;P组给予异丙酚,终浓度16 μg/ml;L组给予溶血磷脂酸,终浓度1 μmol/L;PL组给予异丙酚和溶血磷脂酸,终浓度分别为16 μg/ml、1μmol/L,均孵育24 h.采用细胞划痕实验确定细胞迁移率,Transwell法检测侵袭细胞数,Western blot法检测基质金属蛋白酶（MMP-2）、MMP-9、RhoA及ROCK1的蛋白表达水平.结果 与C组比较,L组细胞迁移率和侵袭细胞数升高,MMP-2、MMP-9、RhoA及ROCK1的蛋白表达上调（P＜0.05）,P组细胞迁移率和侵袭细胞数降低,MMP-2、MMP-9、RhoA及ROCK1的蛋白表达下调（P＜0.05）;与L组比较,PL组细胞迁移率和侵袭细胞数降低,MMP-2、MMP-9、RhoA及ROCK1的蛋白表达下调（P＜0.05）.结论 异丙酚降低人胃癌细胞转移能力的机制与抑制RhoA/ROCK1信号通路有关.Objective To preliminarily evaluate the role of Ras homolog gene （Rho）/Rho-associated coiled coil-forming protein kinase （ROCK） signaling pathway in propofol-induced inhibition of metastasis of human gastric cancer cells.Methods Human gastric cancer MKN-45 cells cultured in vitro,with the concentration of 1.0× 106 cells/ml,were seeded in culture plates,and incubated for 24 h.The plates were then randomly divided into 4 groups using a random number table：control group （group C）,propofol group （group P）,lysophosphatidic acid group （group L） and propofol ＋ lysophosphatidic acid group （group PL）.Group C received no administration.In group P,propofol at the final concentration of 16 μg/ml was given.In group L,lysophosphatidic acid at the final concentration of 1 μmol/L was administered.In group PL,propofol and lysophosphatidic acid were given with the final concentration of 16 μg/ml and 1 μmol/L,respectively.All the cells were then incubated for another 24 h.The migration of cells was determined by wound healing assay,and cell migration rates were calculated.The invasion of cells was determined by Transwell assay,and the invaded cells were counted.The expression of matrix metalloproteinases-2 （MMP-2）,MMP-9,RhoA,and ROCK1 in cells was detected by Western blot.Results Compared with group C,cell migration rates and the number of invaded cells were significantly increased,and the expression of MMP-2,MMP-9,RhoA and ROCK1 was up-regulated in group L,and cell migration rates and the number of invaded cells were decreased,and the expression of MMP-2,MMP-9,RhoA and ROCK1 was down-regulated in group P.Compared with group L,cell migration rates and the number of invaded cells were significantly decreased,and the expression of MMP-2,MMP-9,RhoA and ROCK1 was down-regulated in group PL.Conclusion Inhibition of RhoA/ROCK1 signaling pathway is involved in the mechanism by which propofol decreases metastasis of human gastric cancer cells.

关 键 词：RHO因子 RHO相关激酶类 二异丙酚 胃肿瘤 肿瘤转移 

分 类 号：R735.2[医药卫生—肿瘤]