Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling.

Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling.
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DOI:
10.1038/s41598-017-12855-w
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发表时间:
2017-10-04
期刊:
影响因子:
4.6
通讯作者:
Bao Y
Bao Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu P;Atkinson SJ;Akbareian SE;Zhou Z;Munsterberg A;Robinson SD;Bao Y

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血管生成在肝细胞癌(HCC)中起着重要作用,抑制血管生成是预防和治疗肝癌的关键。膳食植物化学物质萝卜硫素(SFN)以其体外和体内抗癌特性而闻名;但到目前为止,还没有研究关注SFN在HCC肿瘤血管生成中的作用。在本研究中,使用肝癌细胞系HepG 2和人内皮细胞HUVECs的体外细胞模型以及离体和体内模型已被用于研究SFN的抗肿瘤和抗血管生成作用。结果表明,SFN降低HUVEC细胞活力,迁移和管形成,所有这些都是血管生成的重要步骤。更重要的是,SFN能显著抑制HepG 2诱导的HUVEC迁移、粘附和管腔形成,这可能与其抑制HepG 2细胞中STAT 3/HIF-1α/VEGF信号通路有关。此外,在改良的鸡胚绒毛尿囊膜(CAM)试验中,SFN显著降低了HepG 2肿瘤的生长,与肿瘤内HIF-1α和VEGF表达的降低相关。总的来说,这些发现为SFN对HCC肿瘤血管生成以及肿瘤生长的抑制作用提供了新的见解,并表明SFN具有预防和治疗HCC的潜力。
Angiogenesis plays an important role in hepatocellular carcinoma (HCC), the inhibition of which is explored for cancer prevention and treatment. The dietary phytochemical sulforaphane (SFN) is known for its anti-cancer properties in vitro and in vivo; but until now, no study has focused on the role of SFN in HCC tumor angiogenesis. In the present study, in vitro cell models using a HCC cell line, HepG2, and human endothelial cells, HUVECs, as well as ex vivo and in vivo models have been used to investigate the anti-tumor and anti-angiogenic effect of SFN. The results showed that SFN decreased HUVEC cell viability, migration and tube formation, all of which are important steps in angiogenesis. More importantly, SFN markedly supressed HepG2-stimulated HUVEC migration, adhesion and tube formation; which may be due to its inhibition on STAT3/HIF-1α/VEGF signalling in HepG2 cells. In addition, SFN significantly reduced HepG2 tumor growth in a modified chick embryo chorioallantoic membrane (CAM) assay, associated with a decrease of HIF-1α and VEGF expression within tumors. Collectively, these findings provide new insights into the inhibitory effect of SFN on HCC tumor angiogenesis as well as tumor growth, and indicate that SFN has potential for the prevention and treatment of HCC.
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