曲马多联合顺铂对人肺腺癌细胞A549侵袭和迁移的影响

The effects of tramadol combined with cisplatin on invasionon and migration of human lung adenocarcinoma cell A549

目的评价曲马多联合顺铂对人肺腺癌细胞A549侵袭和迁移的影响。方法人肺腺癌细胞A549接种于培养板培养24h,随机分为五组:对照组(CON组),顺铂组(CIS组),3μg/ml曲马多+顺铂组(TT1组),30μg/ml曲马多+顺铂组(TT2组)和300μg/ml曲马多+顺铂组(TT3组),顺铂浓度均为4μg/ml。各组分别加入药物孵育48h后即刻,采用Transwell法检测细胞侵袭能力,细胞划痕实验检测细胞迁移能力,Western blot法检测基质金属蛋白酶-2(MMP-2)、MMP-9、Ezrin蛋白和Fascin蛋白的表达。结果与CON组比较,其余四组肿瘤细胞侵袭和迁移能力明显降低(P<0.05),TT3组MMP-2、MMP-9、Ezrin和Fascin蛋白表达明显下调(P<0.05)。与CIS组比较,TT1组、TT2组和TT3组肿瘤细胞侵袭和迁移能力明显降低(P<0.05),TT3组MMP-2、MMP-9、Ezrin和Fascin蛋白表达明显下调(P<0.05)。结论曲马多剂量依赖性地增强顺铂对人肺腺癌细胞A549的侵袭和迁移的抑制作用,MMP-2、MMP-9、Ezrin和Fascin表达下调可能是其机制之一。

Objective To investigate the effect of tramadol combined with cisplatin on invasion- on and migration of human lung adenocarcinoma cell A549. Methods Human lung adenocarcinoma A549 cells were inoculated on cultured for 24 h, then were randomly divided into 5 groups： control group（group CON）, cisplatin group（group CIS）, tramadol 3 /μg/ml＋eisplatin group（group TT1）, tramadol 30/μg/mlq-cisplatin group（group TT2）, tramadol 300/zg/ml＋cisplatin group（group TT3）. Concentration of cisplatin was 4 /μg/ml. Each group were medicated immediately after 48 h incuba- tion, invasion detection cells by Transwell assay, cell scratch assay cell migration ability, Western- blot detection of matrix metalloproteinase-2 （MMP-2）, the expression of MMP-9, Ezrin protein and Fascin protein. Results Compared with group CON, group CIS and tramadol cmbined with cisplatin group redueced tumor cell invasion and migration ability, group TT3 and CIS up-regulated MMP-2, MMP-9, Ezrin and Fascin expression （P〈0.05）. Compared with group CIS, tramadol combined with cisplatin group reduced tumor cell migration and invasion. Group TT3 down-regulated MMP-2, MMP-9, Ezrin and Fascin expression （P〈0.05）. Conclusion Tramadol could dose-dependently en- hance cisplatin on invasion and migration of human lung adenocarcinoma cell A549, down-regulation MMP-2, MMP-9, Ezrin and Fascin expression is one of its possible mechanisms.