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目的:研究姜黄素抑制血管生成的分子机制。方法:采用MTT法、流式细胞术(FCM)观察姜黄素对人脐静脉内皮细胞(HUVECs)的抑制作用及促凋亡作用。采用RT-PCR法及Western-blot法检测姜黄素作用人肺腺癌A2细胞不同时间后血管生成素(Ang-1、Ang-2)、血小板反应素(TSP)mRNA的表达水平和血管内皮生长因子(VEGF),基质金属蛋白酶(MMP-9)的蛋白表达水平。结果:姜黄素能抑制HUVECs的增殖,呈时间及浓度依赖性,且能诱导HUVECs凋亡,凋亡率明显高于对照组(P<0.01)。A2细胞经100μmol/L姜黄素作用不同时间后Ang-1、Ang-2、TSPmRNA的表达率明显下降;VEGF与MMP-9的蛋白表达也明显减少。结论:姜黄素可能通过下列途径抑制肿瘤的血管生成:1)直接抑制血管内皮细胞增殖并促进其凋亡;2)抑制血管生成促进因子(VEGF,Ang-1,Ang-2)的表达;3)促进血管生成抑制因子TSP的表达;4)降低基质金属蛋白酶MMP-9的活性从而抑制细胞外基质降解。
Objective: To study the molecular mechanism of curcumin in inhibiting angiogenesis. Methods: The inhibitory effect of curcumin on human umbilical vein endothelial cells (HUVECs) was observed by MTT assay and flow cytometry (FCM). The expression of angiopoietin (Ang-1, Ang-2) and thrombospondin (TSP) mRNA and the expression of vascular endothelial growth factor (VEGF) in human lung adenocarcinoma A2 cells were detected by RT-PCR and Western- Factor (VEGF), matrix metalloproteinases (MMP-9) protein expression levels. Results: Curcumin inhibited the proliferation of HUVECs in a time and concentration-dependent manner, and induced the apoptosis of HUVECs. The apoptotic rate of HUVECs was significantly higher than that of the control group (P <0.01). The expression of Ang-1, Ang-2 and TSPmRNA in A2 cells after 100μmol / L curcumin treatment decreased significantly, and the protein expression of VEGF and MMP-9 decreased significantly. Conclusion: Curcumin may inhibit tumor angiogenesis through 1) direct inhibition of vascular endothelial cell proliferation and promote its apoptosis; 2) inhibit the expression of angiogenesis promoting factors (VEGF, Ang-1, Ang-2); 3 ) Promotes the expression of the angiogenesis inhibitor TSP; 4) decreases the activity of the matrix metalloproteinase MMP-9 and thereby inhibits the extracellular matrix degradation.