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目的观察白藜芦醇对肺癌细胞基质金属蛋白酶9(MMP-9)表达的影响,并探讨其可能的分子机制。方法体外培养人小细胞肺癌NCI-H446细胞,用不同浓度的白藜芦醇刺激。小室侵袭实验检测NCI-H446细胞的迁移与侵袭;Western blot检测MMP-9表达以及NF-κB p65亚基核转位;荧光素酶报告基因分析MMP-9和NF-κB活性。结果 50 nM白藜芦醇孵育24 h后,其迁移与侵袭率分别降低了37%和33%;Western blot显示,白藜芦醇能抑制p65核转位;此外,白藜芦醇能以剂量依赖性方式抑制MMP-9的转录活性,NF-κB突变后报告基因活性显著降低。结论白藜芦醇可通过抑制NF-κB介导的MMP表达从而抑制NCI-H446细胞侵袭迁移。
Objective To investigate the effect of resveratrol on the expression of matrix metalloproteinase-9 (MMP-9) in lung cancer cells and to explore its possible molecular mechanism. Methods Human small cell lung cancer NCI-H446 cells were cultured in vitro and stimulated with different concentrations of resveratrol. Cell invasion assay was used to detect the migration and invasion of NCI-H446 cells. Western blot was used to detect the expression of MMP-9 and NF-κB p65 subunit nuclear translocation. Luciferase reporter assay was used to analyze the activity of MMP-9 and NF-κB. Results The migration and invasion of resveratrol after 50 nM incubation for 24 h were reduced by 37% and 33%, respectively. Western blot showed that resveratrol inhibited p65 nuclear translocation. In addition, Dependent transcriptional inhibition of MMP-9 activity, NF-κB mutation significantly decreased the reporter gene activity. Conclusion Resveratrol can inhibit the invasion and migration of NCI-H446 cells by inhibiting the NF-κB-mediated MMP expression.