姜黄素抗血管生成分子机制的探讨

Potential molecular mechanisms behind the anti-angiogenesis effects of Curcumin

  • 摘要: 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。

     

    Abstract: Objective: To investigate the molecular mechanism behind Curcumin's anti-angiogenesis property. Methods: The anti-angiogenesis effect of curcumin on human umbilical vein endothelial cells (HUVEC) was studied using the MTT assay and flow cytometry (FCM). At different timepoints after curcumin treatment, Ang-1, Ang-2 and TSP mRNA levels were detected by RT-PCR and VEGF and MMP-9 protein expression levels were detected by Western blot using human lung adenocarcinoma A2 cells. Results: Curcumin inhibited HUVEC proliferation in a time/dose-dependent manner. Meanwhile,Curcumin induced HUVEC apoptosis, showing a higher apoptosis rate than the control (P<0.01). At different timepoints after curcumin treatment, Ang-1, Ang-2 and TSP mRNA levels and VEGF and MMP-9 protein expression levels in lung adenocarcinoma A2 cells decreased markedly. Conclusion:Curcumin inhibits angiogenesis via the following possible mechanisms: (1) by directly inhibiting vascular endothelial cell proliferation and enhancing cell apoptosis; (2) by inhibiting expression of pro-angio-genesis factors such as VEGF, Ang-1 and Ang-2; (3) by enhancing the expression of TSP, an anti-an-giogenesis factor; (4) by decreasing MMP-9 protein expression, thereby inhibiting extracellular matrix degradation.

     

/

返回文章
返回