Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells
Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells
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DOI：
10.4161/cbt.19599
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发表时间：
2012-05-01
影响因子：
3.6
通讯作者：
Kwon, Sang-Mo
中科院分区：
文献类型：
--
作者：
Kim, Jae-Won;Jung, Seok-Yun;Kwon, Sang-Mo
越来越多的证据表明，人参皂苷Rg 3似乎通过抑制细胞增殖、肿瘤细胞侵袭和转移来抑制肿瘤生长，包括刘易斯肺癌、肠腺癌或B16黑色素瘤。内皮祖细胞（EPCs）似乎在早期肿瘤的生长中起着关键作用，通过干预血管生成开关，在肿瘤进展过程中产生血管生成细胞因子，促进肿瘤新血管形成。本文报道了一种新的抗癌生物分子人参皂苷Rg 3通过抑制EPCs的多种生物活性来抑制肿瘤血管生成的机制。人参皂甙Rg 3对体外培养的内皮细胞的增殖、迁移和小管形成有抑制作用。重要的是，人参皂苷Rg 3在体外减弱了VEGF依赖性p38/ERK信号传导的磷酸化级联反应。异种移植肿瘤模型清楚地表明，人参皂苷Rg 3通过抑制EPCs从骨髓微环境向外周循环的动员来抑制肿瘤生长和肿瘤血管生成，并调节VEGF依赖性肿瘤血管生成。总之，本研究提供了一个潜在的治疗分子，人参皂苷Rg 3，作为一种抗癌药物，通过抑制EPC的生物活性。
Accumulating evidence suggests that Ginsenoside Rg3 appears to inhibit tumor growth including Lewis lung carcinoma, intestinal adenocarcinomas or B16 melanoma by inhibiting cell proliferation, tumor cell invasion and metastasis. Endothelial progenitor cells (EPCs) appear to play a key role in the growth of early tumors by intervening with the angiogenic switch promoting tumor neovessel formation by producing angiogenic cytokines during tumor progression. This paper reports a novel mechanism of Ginsenoside Rg3, a candidate anticancer bio-molecule, on tumor angiogenesis by inhibiting the multiple bioactivities of EPCs. When Ginsenoside Rg3 was applied to the ex vivo cultured outgrowth ECs, a type of EPCs, it inhibited the cell proliferation, cell migration and tubular formation of EPCs. Importantly, Ginsenoside Rg3 attenuated the phosphorylation cascade of the VEGF dependent p38/ERK signaling in vitro. The xenograft tumor model clearly showed that Ginsenoside Rg3 suppresses tumor growth and tumor angiogenesis by inhibiting the mobilization of EPCs from the bone marrow microenvironment to the peripheral circulation and modulates VEGF-dependent tumor angiogenesis. In conclusion, this study provides a potential therapeutic molecule, Ginsenoside Rg3, as an anticancer drug by inhibiting the EPC bioactivities.