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Ginsenoside Rg3 attenuates hepatoma VEGF overexpression after hepatic artery embolization in an orthotopic transplantation hepatocellular carcinoma rat model

Authors Zhou B, Wang J, Yan Z

Received 23 June 2014

Accepted for publication 20 August 2014

Published 21 October 2014 Volume 2014:7 Pages 1945—1954


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr Jianmin Xu

Bo Zhou, Jianhua Wang, Zhiping Yan

Department of Interventional Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, People's Republic of China

Background: Hypoxia-induced vascular endothelial growth factor (VEGF) upregulation and angiogenesis following treatment of hepatocellular carcinoma (HCC) with transarterial embolization (TAE) or transarterial chemoembolization (TACE) may be mediated by ginsenoside Rg3, an anti-angiogenic saponin extracted from ginseng.
Objective: To access the synergistic action of Rg3 and TAE treatment on HCC by VEGF and it's receptor expressions decreasing in a rat model of HCC.
Methods: An orthotopic transplantation HCC model was established in Buffalo rats. HCC rats were treated with hepatic artery infusions of normal saline or iodized oil (0.1 mL) with or without Rg3 (1 mg/kg) (each n=15 in control, Rg3, TAE, and TAE + Rg3 groups). At 1, 2, 4, and 8 weeks, performance status (body weight), tumor progression (longest tumor diameter), metastasis rate, microvessel density (MVD), and overall survival rate were assessed. Additionally, cluster of differentiation 31 (CD31), VEGF, VEGF receptor 2 (VEGF-R2) and VEGF-R2 phosphorylation levels were assessed by immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blot.
Results: Combined Rg3 and TAE treatment reduced tumor progression, body weight loss, angiogenesis, and metastasis rate, and led to better overall survival in the HCC rat model. ELISA results showing VEGF expression in the control, Rg3, TAE, and TAE + Rg3 groups at 4 weeks following treatment were 132.6±2.38, 37.9±0.8, 87.4±0.7, and 45.3±0.4 pg/mL, respectively. Combined Rg3 and TAE reduced the protein expression of CD31 and VEGF-R2 phosphorylation, compared with those in the TAE group at 4 weeks of treatment.
Conclusion: Combined Rg3 and TAE treatment limited metastasis and promoted survival by downregulating VEGF overexpression in HCC tumors. Thus, this treatment may have potential clinical implications for HCC patients undergoing TAE or TACE.

Keywords: ginsenoside Rg3, vascular endothelial growth factor, hepatocellular carcinoma, angiogenesis, hypoxia

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