目的:探讨马钱子碱抑制环氧化酶2(COX-2),从而诱导非小细胞肺癌细胞凋亡的分子机制。方法:构建COX-2启动子若干转录因子缺失突变体与含COX-2 mRNA 3’-UTR的报告质粒,与Renillia共转染至非小细胞肺癌A549细胞,测报告基因luciferase活性研究COX-2启动子受马钱子碱抑制的最小顺式作用元件;采用蛋白质免疫印迹法研究马钱子碱对IκBα磷酸化与p65进核的影响。结果:马钱子碱显著性抑制LPS诱导的COX-2启动子的激活,而对COX-2 mRNA转录后调控影响不大,COX-2启动子-262位附近NF-κB是马钱子碱抑制COX-2启动子活性的重要顺式作用元件。马钱子碱能抑制IκBα的磷酸化,并能抑制p65的进核。结论:马钱子碱抑制NF-κB的激活,进而从转录水平COX-2的基因表达,促进A549细胞凋亡。 AIM: To investigate the molecular mechanism of brucine in inhibiting cyclooxygenase 2 (COX-2) and inducing apoptosis in non-small cell lung cancer cells. METHODS: Several transcriptional variants of COX-2 promoter were constructed and reporter plasmids containing 3’-UTR of COX-2 mRNA were co-transfected into non-small cell lung cancer A549 cells with Renillia and the reporter gene luciferase activity was assayed. COX-2 The promoter was minimal cis-acting element inhibited by brucine. Western blotting was used to study the effect of brucine on IκBα phosphorylation and p65 entry. RESULTS: Brucine significantly inhibited the activation of COX-2 promoter induced by LPS, but had little effect on the post-transcriptional regulation of COX-2 mRNA. NF-κB in the vicinity of COX-2 promoter was strychnine Important cis-acting element that inhibits COX-2 promoter activity. Strychnine can inhibit IκBα phosphorylation, and can inhibit p65 into the nucleus. Conclusion: Strychnine can inhibit the activation of NF-κB, and further promote the apoptosis of A549 cells through the gene expression of COX-2 at transcriptional level.