title: Ginsenoside Rg3 inhibition of vasculogenic mimicry in pancreatic cancer through downregulation of VE‑cadherin/EphA2/MMP9/MMP2 expression.
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.
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Jing-Qiang
authors.initials: JQ
authors.lastname: Guo
authors.affiliation: Guangxi Medical University, Nanning 530021, P.R. China.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Zheng
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Jin-Bo
authors.initials: JB
authors.lastname: Xu
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Min-Yuan
authors.initials: MY
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Dian
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, P.R. China.
authors.forename: Shengzhang
authors.initials: S
authors.lastname: Lin
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010182:Pancreatic Diseases / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D036104:Receptor, EphA2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D000970:Antineoplastic Agents; D015820:Cadherins; D036145:Ginsenosides; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D036104:Receptor, EphA2; D000099152:Cadherin 5; C097367:ginsenoside Rg3