Kim Seo Ho, Kim Eok-Cheon, Kim Wan-Joong, Lee Myung-Hun, Kim Sun-Young, Kim Tack-Joong
a Yonsei-Fraunhofer Medical Device Lab, Division of Biological Science and Technology , College of Science and Technology, Yonsei University , Wonju , Korea.
Biosci Biotechnol Biochem. 2016 Jun;80(6):1095-106. doi: 10.1080/09168451.2016.1148574. Epub 2016 Feb 29.
Angiogenesis, neovascularization from pre-existing vessels, is a key step in tumor growth and metastasis, and anti-angiogenic agents that can interfere with these essential steps of cancer development are a promising strategy for human cancer treatment. In this study, we characterized the anti-angiogenic effects of Coptis japonica Makino extract (CJME) and its mechanism of action. CJME significantly inhibited the proliferation, migration, and invasion of vascular endothelial growth factor (VEGF)-stimulated HUVECs. Furthermore, CJME suppressed VEGF-induced tube formation in vitro and VEGF-induced microvessel sprouting ex vivo. According to our study, CJME blocked VEGF-induced cell cycle transition in G1. CJME decreased expression of cell cycle-regulated proteins, including Cyclin D, Cyclin E, Cdk2, and Cdk4 in response to VEGF. Taken together, the results of our study indicate that CJME suppresses VEGF-induced angiogenic events such as proliferation, migration, and tube formation via cell cycle arrest in G1.
血管生成,即从已有的血管形成新血管,是肿瘤生长和转移的关键步骤,能够干扰癌症发展这些关键步骤的抗血管生成剂是一种很有前景的人类癌症治疗策略。在本研究中,我们对黄连提取物(CJME)的抗血管生成作用及其作用机制进行了表征。CJME显著抑制血管内皮生长因子(VEGF)刺激的人脐静脉内皮细胞(HUVECs)的增殖、迁移和侵袭。此外,CJME在体外抑制VEGF诱导的管腔形成,在体内抑制VEGF诱导的微血管芽生。根据我们的研究,CJME阻断了VEGF诱导的G1期细胞周期转变。CJME降低了细胞周期调节蛋白的表达,包括对VEGF作出反应的细胞周期蛋白D、细胞周期蛋白E、细胞周期蛋白依赖性激酶2(Cdk2)和细胞周期蛋白依赖性激酶4(Cdk4)。综上所述,我们的研究结果表明,CJME通过G1期细胞周期阻滞抑制VEGF诱导的血管生成事件,如增殖、迁移和管腔形成。