TrkB影响结肠癌细胞SW620侵袭能力及与ERK信号通路活化关系的研究  

Effect of TrkB on the invasion of SW620 colon cancer cells correlates with the activation of ERK signaling pathway

作　　者：马思平[1] 王永鹏[2] 张菁茹[2] 张庆彤[2] 单吉贤[1] 

机构地区：[1]中国医科大学附属第一医院肿瘤外科,辽宁沈阳110001 [2]辽宁省肿瘤医院外一科,辽宁沈阳110042

出　　处：《中国现代普通外科进展》2013年第6期426-431,共6页Chinese Journal of Current Advances in General Surgery

摘　　要：目的:探讨干扰结肠癌细胞TrkB蛋白表达及抑制ERK活化对细胞增殖、凋亡和侵袭以及细胞内ERK磷酸化水平的影响。方法:应用特异性TrkB-siRNA瞬时转染及ERK特异性抑制剂处理SW620结肠癌细胞,观察SW620细胞增殖、凋亡和侵袭情况以及细胞内ERK磷酸化水平的变化。结果:特异性siRNA转染高表达TrkB的SW620细胞,TrkB蛋白表达减少,ERK的磷酸化水平降低,且转染组细胞数显著低于对照组(P=0.001),转染组的细胞凋亡率显著高于对照组(P=0.000 1),24 h后侵袭至下层小室的细胞数转染组显著低于对照组(P=0.001);ERK抑制剂明显降低SW620细胞ERK磷酸化水平(P=0.001),而对ERK蛋白表达没有影响,且应用ERK抑制剂作用SW620细胞,对照组和处理组中细胞数没有显著差异(P=0.544),对照组和处理组中SW620细胞的凋亡率差异无统计学意义(P=0.103),但对照组24 h后侵袭至下层小室的细胞数显著高于处理组(P=0.0001)。结论:干扰TrkB蛋白表达能够降低高转移结肠腺癌SW620细胞内ERK磷酸化水平,促进细胞凋亡并抑制细胞增殖和侵袭。同时应用ERK特异性抑制剂也显著抑制细胞侵袭。因此ERK信号转导通路可能与TrkB介导的结肠腺癌细胞抗凋亡和侵袭能力的增加相关,沉默TrkB表达可能成为阻断结肠癌转移的新靶点。Objective： To investigate the effects of reducing the expression of TrkB protein of colon cancer cells and inhibiting the ERK activation on cell proliferation,apoptosis and invasion and intracellular ERK phosphorylation levels.Methods： Specific TrkB-siRNA transient transfection and the ERK inhibitor were used to treat SW620 colon cancer cells,and then SW620 cell proliferation,apoptosis and cell invasion as well as changes in the level of ERK phosphorylation were observed.Results： SW620 cells of overexpression of TrkB were transfected with specific siRNA.The results showed that TrkB protein expression was decreased,ERK phosphorylation were reduced and the cell number of transfection group was significantly lower than that of control group（P=0.001）,but apoptosis rates of transfection group were significantly higher than that of control group（P=0.0001）,the cell number of transfection group invading to the lower chamber after 24hours was significantly lower than that of control group（P=0.001）,ERK inhibitor significantly decreasd the level of ERK phosphorylation of SW620 cells,but there was no effect on the expression of ERK.There was no difference of cell numbe（r P=0.544）and apoptosis rates（P=0.103）between control and treatment groups after SW620 cells were treated with ERK inhibitor,but the cell number of treatment group invading to the lower chamber after 24hours was significantly lower than that of control group（P=0.0001）.Conclusion： Blocking TrkB expression by TrkB-siRNA promoted apoptosis,inhibited proliferation and invasion of SW620 cells and ERK activation.ERK signaling may play a role in TrkB-mediated the increased abilities of apoptosis-resist and invasion of SW620 cells.

关 键 词：结肠肿瘤 TrkB蛋白 细胞转染 ERK信号通路 

分 类 号：R735.35[医药卫生—肿瘤]