Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, PR China.
Mol Med Rep. 2011 Nov-Dec;4(6):1283-8. doi: 10.3892/mmr.2011.577. Epub 2011 Aug 31.
Inhibition of tumor angiogenesis has become an attractive target of anticancer chemotherapy. However, drug resistance and cytotoxicity against non-tumor associated endothelial cells limit the long-term use and the therapeutic effectiveness of angiogenesis inhibitors, thus increasing the necessity for the development of multi-target agents with minimal side effects. Traditional Chinese medicine (TCM) formulas, which have relatively fewer side effects and have been used clinically to treat various types of diseases, including cancer, for thousands of years, are considered to be multi-component and multi-target agents exerting their therapeutic function in a more holistic way. Hedyotis Diffusa Willd (EEHDW) has long been used as an important component in several TCM formulas to treat various types of cancer. Although recently we reported that EEHDW promotes cancer cell apoptosis via activation of the mitochondrial-dependent pathway, the precise mechanism of its tumoricidalactivity still remains to be clarified. In the present study, we investigated the angiogenic effects of the ethanol extract of EEHDW. Cell cycle analysis was perfomed using flow cytometry. Cell viability was analyzed using MTT assay. We found that EEHDW inhibited angiogenesis in vivo in chick embryo chorioallantoic membrane (CAM). In addition, we observed that EEHDW dose- and time-dependently inhibited the prolife-ration of human umbilical vein endothelial cells (HUVEC) by blocking the cell cycle G1 to S progression. Moreover, EEHDW inhibited the migration and tube formation of HUVECs. Furthermore, EEHDW treatment down-regulated the mRNA and protein expression levels of VEGF-A in HT-29 human colon carcinoma cells and HUVECs. Our findings suggest that inhibiting tumor angiogenesis is one of the mechanisms by which EEHDW is involved in cancer therapy.
抑制肿瘤血管生成已成为抗癌化疗的一个有吸引力的靶点。然而，药物耐药性和对非肿瘤相关内皮细胞的细胞毒性限制了血管生成抑制剂的长期使用和治疗效果，因此增加了开发具有最小副作用的多靶点药物的必要性。中药（TCM）配方具有相对较少的副作用，并且已经在临床上用于治疗各种类型的疾病，包括癌症，已经使用了数千年，被认为是多成分和多靶点药物，以更全面的方式发挥其治疗功能。白花蛇舌草（EEHDW）长期以来一直被用作几种 TCM 配方的重要成分，用于治疗各种类型的癌症。尽管最近我们报道 EEHDW 通过激活线粒体依赖性途径促进癌细胞凋亡，但它的杀肿瘤活性的确切机制仍有待阐明。在本研究中，我们研究了 EEHDW 乙醇提取物的血管生成作用。使用流式细胞术进行细胞周期分析。使用 MTT 分析检测细胞活力。我们发现 EEHDW 在鸡胚绒毛尿囊膜（CAM）中体内抑制血管生成。此外，我们观察到 EEHDW 通过阻断细胞周期 G1 到 S 进展，剂量和时间依赖性地抑制人脐静脉内皮细胞（HUVEC）的增殖。此外，EEHDW 抑制 HUVEC 的迁移和管形成。此外，EEHDW 处理下调 HT-29 人结肠癌细胞和 HUVEC 中 VEGF-A 的 mRNA 和蛋白表达水平。我们的研究结果表明，抑制肿瘤血管生成是 EEHDW 参与癌症治疗的机制之一。
