An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis
An oriental herbal cocktail, ka-mi-kae-kyuk-tang, exerts anti-cancer activities by targeting angiogenesis, apoptosis and metastasis
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DOI：
10.1093/carcin/bgl104
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发表时间：
2006-12-01
期刊：
影响因子：
4.7
通讯作者：
Kim, Sung-Hoon
中科院分区：
文献类型：
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作者：
Lee, Hyo-Jeong;Lee, Eun-Ok;Kim, Sung-Hoon
严格和系统的临床前研究对于确定东方草药和配方的有效性和安全性是必要和必不可少的，以便将传统草药实践转化为循证医学。在这里，我们评估了Ka-mi-kae-kyuk-tang（KMKKT），10个东方草药配方的乙醇提取物的抗癌活性，在体外和体内的机制为基础的生物标志物，涉及血管生成，细胞凋亡和转移电池。结果显示，KMKKT通过抑制人脐静脉内皮细胞模型中碱性成纤维细胞生长因子（bFGF）诱导的ERK 1/2磷酸化、细胞迁移以及管形成来抑制血管内皮反应，并且在体外降低小鼠刘易斯肺癌（LLC）细胞中缺氧诱导的HIF 1 α和血管上皮生长因子（VEGF）表达，在鸡胚绒毛尿囊膜模型和小鼠Matrigel塞中，抑制bFGF诱导的血管生成。腹腔注射KMKKT可有效抑制同系小鼠皮下接种LLC细胞的生长。此外，KMKKT在体外抑制小鼠结肠癌26-L5细胞的侵袭能力，并减少其门静脉接种在同系小鼠中的肝转移形成。此外，KMKKT抑制了无胸腺裸鼠中人PC-3前列腺癌异种移植物的生长，并避免了癌症相关的体重减轻。体内肿瘤生长抑制与微血管密度和VEGF丰度降低以及PARP裂解增加和TUNEL阳性细胞凋亡相关。总之，我们的数据支持KMKKT靶向血管生成、细胞凋亡和转移的广谱体内抗癌活性，而对体重没有任何不良影响。该配方值得认真考虑，以进一步评价多器官部位癌症的化学预防和治疗。
Rigorous and systematic pre-clinical studies are necessary and essential to establish the efficacy and safety of Oriental herbs and formulas in order to transform traditional herbal practices into evidence-based medicine. Here we evaluated the anti-cancer activities of the ethanol extract of Ka-mi-kae-kyuk-tang (KMKKT), a formula of ten Oriental herbs, with a battery of in vitro and in vivo mechanism-based biomarkers involving angiogenesis, apoptosis and metastasis. The results show that KMKKT suppressed the vascular endothelial responses by inhibiting basic fibroblast growth factor (bFGF)-induced ERK1/2 phosphorylation, cell migration as well as tube formation in the human umbilical vein endothelial cell model, and decreased the hypoxia-induced HIF1 alpha and vascular epithelial growth factor (VEGF) expression in the mouse Lewis lung carcinoma (LLC) cells in vitro, and inhibited the bFGF-induced angiogenesis in chick chorioallantoic membrane model, and in the Matrigel plugs in mice. Intraperitoneal delivery of KMKKT potently inhibited the growth of the subcutaneously inoculated LLC cells in syngenic mice. In addition, KMKKT inhibited the invasion ability of the mouse colon 26-L5 cancer cells in vitro and decreased their formation of liver metastasis when intraportally inoculated in syngenic mice. Furthermore, KMKKT suppressed the growth of the human PC-3 prostate cancer xenografts in athymic nude mice and averted the cancer-related body weight loss. The in vivo cancer growth suppression was associated with a decreased microvessel density and VEGF abundance as well as an increased PARP cleavage and the TUNEL-positive apoptosis. Together, our data support broad-spectra in vivo anti-cancer activities of KMKKT targeting angiogenesis, apoptosis and metastasis without any adverse effect on the body weight. This formula merits serious consideration for further evaluation for the chemoprevention and treatment of cancers of multiple organ sites.