胡椒碱联合顺铂对肺腺癌A549细胞生长及MMP-2、VEGF的影响

Effect of piperine combined with cisplation on proliferation and MMP-2,VEGF of human lung adenocarcinoma A549 cell

目的:研究胡椒碱与顺铂联合对肺腺癌A549细胞生长和凋亡的作用,以及检测A549细胞基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达水平。方法:MTT法检测不同质量浓度的胡椒碱、顺铂及两者联合对A549细胞增殖的影响。流式细胞术分析细胞凋亡。RT-PCR测定各组A549细胞MMP-2 mRNA和VEGF mRNA的表达变化。结果:胡椒碱与顺铂均可抑制人肺腺癌A549细胞的生长,呈时间—浓度依赖性(P<0.05);联合组随作用时间延长,对A549细胞的抑制效应增加(P<0.05)。联合组较对照组、胡椒碱组、顺铂组的A549细胞凋亡率显著增高(P<0.05)。联合组与对照组及单用胡椒碱、顺铂比较,MMP-2 mRNA和VEGF mRNA的表达明显下调(P<0.05)。结论:胡椒碱显著提高顺铂对肺腺癌A549细胞的生长抑制和促进凋亡效应,降低MMP-2、VEGF的表达,从而可能抑制肺癌细胞的迁移。

Objective： To investigate the proliferation and apoptosis of piperine combined with cisplation on A549 cells and the changes in the expression of MMP-2 and VEGF. Methods： MTT assay was used to detect the proliferation on A549 cells after treatment with series of monotherapy group（ piperine or cisplation alone） or combination group（ piperine combined with cisplation）. Flow cytometry was performed to assess the cellular apoptosis. The expression of MMP-2,VEGF mRNA were measured by RT-PCR in each group. Results： Both piperine and cisplation could inhibit the growth of A549 cells in a time-dose dependent manner（ P〈0. 05）. With the increasing time,the cell proliferation was significantly inhibited in the combination group（ P〈0. 05）. The combination group also showed an obviously higher apoptosis rate than piperine alone,cisplation alone and control group,respectively（ P〈0. 05）. In addition,the expression of MMP-2 and VEGF mRNA in combination group were evidently lower than that of monotherapy group and control group（ P〈0. 05）. Conclusion： Piperine can evidently enhance the anti-proliferation and induce apoptosis effect of cisplation in A549 cells,as well as decrease the level of MMP-2 and VEGF mRNA,thus suppress cancer metastasis.