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人参葡萄糖基齐墩果酸酯通过PI3K/AKT/HIF-1α通路抑制宫颈癌细胞增殖和血管生成。

Ginseng glucosyl oleanolate inhibit cervical cancer cell proliferation and angiogenesis via PI3K/AKT/HIF-1α pathway.

作者信息

Liu Sitong, Ai Zhiyi, Hu Yue, Ren Guangquan, Zhang Junshun, Tang Ping, Zou Hongyang, Li Xia, Wang Yu, Nan Bo, Wang Yuhua

机构信息

College of Food Science and Engineering, Jilin Agricultural University, Changchun, China.

Jilin Province Innovation Center for Food Biological Manufacture, Jilin Agricultural University, Changchun, China.

出版信息

NPJ Sci Food. 2024 Dec 19;8(1):105. doi: 10.1038/s41538-024-00341-3.

Abstract

Ginseng (Panax ginseng C.A. Meyer) is widely used in several functional foods at present. Ginsenosides, is the most crucial bioactive constituents in ginseng whose antitumor activity have been widely reported. In this study, the effect of ginseng glucosyl oleanolate (GGO) produced from ginsenoside Ro through enzymatic transformation, on cervical cancer was evaluated in vitro and in vivo. GGO significantly inhibited the viability and colony forming ability of HeLa cells, and blocked the cell cycle in G0/G1 phase, which showed its ability to inhibit the proliferation of HeLa cells. GGO exhibited anti-angiogenesis effect in HUVECs, chick chorioallantoic membrane (CAM) and Matrigel plugs model. These effects were related to interference with the paracrine axis of VEGF/VEGFR2 and blockage of the downstream PI3K/AKT/HIF-1α signaling pathway of the autocrine axis. The dual inhibitory effects of GGO were also exhibited in immunocompromised mice undergoing heterograft and suppressed tumor growth without any side effects. These findings provide a theoretical basis for further development of GGO as a functional food with anti-tumor properties.

摘要

人参(Panax ginseng C.A. Meyer)目前广泛应用于多种功能性食品中。人参皂苷是人参中最关键的生物活性成分,其抗肿瘤活性已被广泛报道。在本研究中,对通过酶促转化人参皂苷Ro产生的人参糖基齐墩果酸酯(GGO)在体外和体内对宫颈癌的作用进行了评估。GGO显著抑制HeLa细胞的活力和集落形成能力,并将细胞周期阻滞在G0/G1期,显示出其抑制HeLa细胞增殖的能力。GGO在人脐静脉内皮细胞(HUVECs)、鸡胚绒毛尿囊膜(CAM)和基质胶栓塞模型中表现出抗血管生成作用。这些作用与干扰VEGF/VEGFR2旁分泌轴以及阻断自分泌轴下游的PI3K/AKT/HIF-1α信号通路有关。GGO的双重抑制作用在接受异种移植的免疫缺陷小鼠中也有体现,且能抑制肿瘤生长而无任何副作用。这些发现为进一步开发具有抗肿瘤特性的功能性食品GGO提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10e3/11659631/f3dc61a69940/41538_2024_341_Fig1_HTML.jpg

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