丹参酮ⅡA对乳腺癌细胞MDA-MB435迁移及肿瘤血管生成的影响

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目的:研究丹参酮ⅡA抑制迁移以及新生血管形成的作用机制.方法:通过MTT,2-D/3-D迁移,血管生成,PCR,CAM等方法,评价丹参酮ⅡA抑制肿瘤细胞增殖,迁移以及新生血管的药理学活性,探讨其可能的作用机制.结果:给药24 h后,丹参酮ⅡA能够抑制乳腺癌细胞(MDA-MB-435)增殖(IC_(50)=21 nmol/mL),并且当浓度分别大于5 nlnoL/mL和6 nmol/mL时,对癌细胞的2-D和3-D迁移具有很好的抑制作用.但其对新生牛主动脉内皮细胞(NCAEC)增殖几乎没有影响(IC_(50)=124 nmol/mL).共培养法tube formation实验发现,丹参酮ⅡA抑制新生血管形成主要作用其第2阶段,即内皮细胞的分化阶段.在基因转录水平上,丹参酮ⅡA对肿瘤增殖、迁移以及血管生成相关基因VEGF,c-Myc及HIF-1α表达具有良好的抑制作用.CAM实验表明,丹参酮ⅡA对新生血管生成也有良好的抑制作用.结论:丹参酮ⅡA具有很好的抑制肿瘤增殖,迁移及血管生成作用.其可能的作用机制是通过抑制VEGF、c-Myc及HIF-1α的表达,从而产生药理学活性.“,”Aim: To investigate the mechanism of anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Methods: In this study, MTT, 2-D/3-D migration, tube formation, PCR, chick embryo chorioallan-toic membrane (CAM) were used to evaluate the anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Results: Tanshinone ⅡA significantly inhibited the proliferation of human breast cancer line MDA-MB-435 with an IC_(50) of 21 nmol/mL And it is showed that breast cancer cells migration was effectively prevented by tanshinone ⅡA at 5 and 6 nmol/mL in a wound healing assay and a transwell migration assay. In ad-dition, tanshinone ⅡA inhibited the tube formation of newborn cattle aortic endothelial cells( NCAECs) after 2 h co-incubation with MDA-MB-435. These effects were not due to the inhibition of NCAECs proliferation; because tanshinone ⅡA non-selectively inhibited NCAECs growth with an IC_(50) of 124 nmol/mL Tanshinone ⅡA showed dose-dependent inhibitory effects on mRNA expression of VEGF and two transcription factors (HIF-1α/c-Myc) . Tashinone ⅡA was also found to inhibit angiogenic in vivo in the CAM assay. Conclusion: These results suggest that tanshinone ⅡA may exert its anti-proliferation, anti-migration and anti-angiogenic effects through down-regu-lating two transcription factors and VEGF. These novel anti-proliferations, anti-migrations, anti-angiogenic activi-ties of tanshinone ⅡA are likely to contribute to its cancer chemopreventive and therapeutic potential, especially in the treatment of breast cancer.
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