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人参皂苷Rg3通过下调VE-钙黏蛋白/EphA2/基质金属蛋白酶9/基质金属蛋白酶2的表达抑制胰腺癌中的血管生成拟态。

Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE‑cadherin/EphA2/MMP9/MMP2 expression.

作者信息

Guo Jing-Qiang, Zheng Qing-Hui, Chen Hui, Chen Liang, Xu Jin-Bo, Chen Min-Yuan, Lu Dian, Wang Zhao-Hong, Tong Hong-Fei, Lin Shengzhang

机构信息

Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.

Guangxi Medical University, Nanning 530021, P.R. China.

出版信息

Int J Oncol. 2014 Sep;45(3):1065-72. doi: 10.3892/ijo.2014.2500. Epub 2014 Jun 16.

DOI:10.3892/ijo.2014.2500
PMID:24938458
Abstract

Ginsenoside Rg3 (Rg3), a trace tetracyclic triterpenoid saponin, is extracted from ginseng and shown to have anticancer activity against several types of cancers. This study explored the effect of Rg3 on pancreatic cancer vasculogenic mimicry. Altered vasculogenic mimicry formation was assessed using immunohistochemistry and PAS staining and associated with the expression of vascular endothelial-cadherin (VE-cadherin), epithelial cell kinase (EphA2), matrix metalloproteinase (MMP)-2 and MMP-9. The effect of Rg3 on the regulation of pancreatic cancer vasculogenic mimicry was evaluated in vitro and in vivo. The data showed vasculogenic mimicry in pancreatic cancer tissues. In addition, the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 proteins associated with formation of pancreatic cancer vasculogenic mimicry. Rg3 treatment reduced the levels of vasculogenic mimicry in nude mouse xenografts in vitro and in vivo, while the expression of VE-cadherin, EphA2, MMP-2 and MMP-9 mRNA and proteins was downregulated by Rg3 treatment in vitro and in tumor xenografts. In conclusion, ginsenoside Rg3 effectively inhibited the formation of pancreatic cancer vasculogenic mimicry by downregulating the expression of VE-cadherin, EphA2, MMP9 and MMP2. Further studies are required to evaluate ginsenoside Rg3 as an agent to control pancreatic cancer.

摘要

人参皂苷Rg3(Rg3)是一种微量四环三萜皂苷,从人参中提取,已显示出对多种癌症具有抗癌活性。本研究探讨了Rg3对胰腺癌血管生成拟态的影响。使用免疫组织化学和PAS染色评估血管生成拟态的改变,并与血管内皮钙黏蛋白(VE-钙黏蛋白)、上皮细胞激酶(EphA2)、基质金属蛋白酶(MMP)-2和MMP-9的表达相关联。在体外和体内评估了Rg3对胰腺癌血管生成拟态调节的影响。数据显示胰腺癌组织中存在血管生成拟态。此外,VE-钙黏蛋白、EphA2、MMP-2和MMP-9蛋白的表达与胰腺癌血管生成拟态的形成相关。Rg3处理在体外和体内均降低了裸鼠异种移植瘤中血管生成拟态的水平,而在体外和肿瘤异种移植瘤中,Rg3处理下调了VE-钙黏蛋白、EphA2、MMP-2和MMP-9的mRNA和蛋白表达。总之,人参皂苷Rg3通过下调VE-钙黏蛋白、EphA2、MMP9和MMP2的表达有效抑制了胰腺癌血管生成拟态的形成。需要进一步研究以评估人参皂苷Rg3作为控制胰腺癌的药物。

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