新型靶向药物索拉菲尼对黑色素瘤细胞株A375细胞增殖及迁移能力影响的研究  

Effects of novel target agent sorafenib on the proliferation and migration of human melanoma cell A375

作　　者：陆群英[1] 许雪[1] 吴原[1] 刘明章[1] 钟华杰[1] 戴利成[2] 宋颖劼[1] 

机构地区：[1]浙江省湖州市中心医院皮肤科,313000 [2]浙江省湖州市中心医院中心实验室,313000

出　　处：《全科医学临床与教育》2015年第4期376-379,389,共5页Clinical Education of General Practice

基　　金：浙江省湖州市科技局一般项目(2011C33063;2012YS09)

摘　　要：目的探讨新型靶向药物索拉菲尼在体外对人黑色素瘤细胞株A375细胞增殖及迁移能力的影响。方法采用阿尔玛蓝法检测索拉菲尼对A375细胞增殖的影响,用划痕法检测索拉菲尼对A375细胞迁移的影响,并通过荧光定量PCR法及Western blot法检测细胞增殖及迁移相关因子MEK及ERK m RNA及蛋白表达。结果 24 h、48 h、72 h、96 h时,1 mol/L、5 mol/L和10 mol/L索拉菲尼组对A375细胞增殖抑制程度均明显大于DMSO对照组,差异有统计学意义(t分别=6.30、9.26、13.45;6.65、9.41、13.73;8.25、12.71、5.09;7.87、13.42、18.62,P均<0.05)。2 h、4 h、8 h、12 h时,5 mol/L、10 mol/L索拉菲尼组对A375细胞迁移抑制程度均明显大于DMSO对照组,差异有统计学意义(t分别=7.23、7.73;7.56、8.62;7.93、15.01;13.25、21.29,P均<0.05)。2 h、4 h、8 h时,1 mol/L、5 mol/L、10 mol/L索拉菲尼对MER m RNA、ERK m RNA的表达比较,差异没有统计学意义(F分别=1.18、1.71、0.28;0.03、0.03、0.03,P均>0.05)。索拉菲尼处理A375细胞后,MER、ERK以及磷酸化的MER、ERK都受到了不同程度的抑制。结论索拉菲尼对体外培养的人黑色素瘤细胞A375的增殖及迁移具有明显的抑制作用,其可能是通过干扰MEK/ERK信号通路而发生的。Objective To investigate the effects of new targeted agent sorafenib on the proliferation and migration of hu-man melanoma cell line A375 in vitro. Methods Alamar Blue assay was performed to detect the proliferation of A375 cells, the wound healing assay was performed to detect the migration of A375 cells, and the m RNA and protein expressions of MEK and ERK were detected by FQ-PCR and western bolt. Results The A375 cell proliferation inhibition that dealt with 1 mol/L,5 mol/L and 10 mol/L sorafenib were significantly greater than the DMSO control group at 24-hour, 48-hour,72-hour and 96-hour（t=6.30,9.26,13.45;6.65,9.41,13.73;8.25,12.71,5.09;7.87,13.42,18.62,P〈0.05）. The A375 cell migration inhibition that dealt with 5mol/L and 10mol/L sorafenib were significantly greater than the DMSO control group at2-hour, 4-hour, 8-hour and 12-hour（t =7.23,7.73; 7.56,8.62; 7.93,15.01;13.25,21.29,P〈0.05）. There was no statistically significant difference of the MER and ERK m RNA expressions among 1mol/L,5mol/L and 10mol/L sorafenib at2-hour, 4-hour and 8-hour（F=1.18,1.71,0.28;0.03,0.03,0.03,P〉0.05）. The expressions of MEK, ERK, p-MEK and p-ERK were inhibited of varying degree after sorafenib treatment. Conclusions Sorafenib has a significant inhibitory effect on the proliferation and migration of human melanoma cell A375, which may be incurred via interfering with MEK/ERK signaling pathway.

关 键 词：索拉菲尼 黑色素瘤 细胞增殖 细胞迁移 

分 类 号：R739.5[医药卫生—肿瘤]