Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis

Aim. Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction an...

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Main Authors: Shen Hu, Yan Zhu, Xiangyang Xia, Xiaobo Xu, Fen Chen, Xudong Miao, Xinmei Chen
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Analytical Cellular Pathology
Online Access:http://dx.doi.org/10.1155/2019/3815786
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author Shen Hu
Yan Zhu
Xiangyang Xia
Xiaobo Xu
Fen Chen
Xudong Miao
Xinmei Chen
author_facet Shen Hu
Yan Zhu
Xiangyang Xia
Xiaobo Xu
Fen Chen
Xudong Miao
Xinmei Chen
author_sort Shen Hu
collection DOAJ
description Aim. Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction and antiangiogenesis effect of Rg3 on orthotopic HCC in vivo. Methods. The murine HCC cells Hep1-6 were implanted in the liver of mouse. With oral feeding of Rg3 (10 mg/kg once a day for 30 days), the quantitative analysis of apoptosis was performed by using pathology and a transmission electron microscope and microvessel density was quantitatively measured by immunohistochemical staining of the CD105 antibody. The mice treated with Rg3 (n=10) were compared with the control (n=10) using Kaplan-Meier analysis. Animal weight and tumor weight were measured to determine the toxicity of Rg3 and antitumor effect on an orthotopic HCC tumor model. Results. With oral feeding of Rg3 daily in the first 30 days on tumor implantation, Rg3 significantly decreased the orthotopic tumor growth and increased the survival of animals (P<0.05). Rg3-treated mice showed a longer survival than the control (P<0.05). Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor apoptotic progress, which then weakened the tumor volume and its capability to produce the vascularized network for further growth of the tumor and remote metastasis. Conclusion. Rg3 inhibited the activation of microtumor vessel formation in vivo besides its apoptosis induction. Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen.
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spelling doaj-art-3eed034bd37c43c9a15c69b63a017c0d2025-08-20T03:35:54ZengWileyAnalytical Cellular Pathology2210-71772210-71852019-01-01201910.1155/2019/38157863815786Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting AngiogenesisShen Hu0Yan Zhu1Xiangyang Xia2Xiaobo Xu3Fen Chen4Xudong Miao5Xinmei Chen6Department of Obstetrics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Respiratory Hangzhou Shulan Hospital, Hangzhou 310009, ChinaDepartment of Ultrasound, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang Province, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang Province, ChinaThe Department of Orthopedics, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310003, ChinaThe Department of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250014 Shandong Province, ChinaAim. Microvessel density is a marker of tumor angiogenesis activity for development and metastasis. Our preliminary study showed that ginsenoside Rg3 (Rg3) induces apoptosis in hepatocellular carcinoma (HCC) in vitro. The aim of this study was to investigate the cross-link for apoptosis induction and antiangiogenesis effect of Rg3 on orthotopic HCC in vivo. Methods. The murine HCC cells Hep1-6 were implanted in the liver of mouse. With oral feeding of Rg3 (10 mg/kg once a day for 30 days), the quantitative analysis of apoptosis was performed by using pathology and a transmission electron microscope and microvessel density was quantitatively measured by immunohistochemical staining of the CD105 antibody. The mice treated with Rg3 (n=10) were compared with the control (n=10) using Kaplan-Meier analysis. Animal weight and tumor weight were measured to determine the toxicity of Rg3 and antitumor effect on an orthotopic HCC tumor model. Results. With oral feeding of Rg3 daily in the first 30 days on tumor implantation, Rg3 significantly decreased the orthotopic tumor growth and increased the survival of animals (P<0.05). Rg3-treated mice showed a longer survival than the control (P<0.05). Rg3 treatment induced apoptosis and inhibited angiogenesis. They contributed to the tumor shrinkage. Rg3 initialized the tumor apoptotic progress, which then weakened the tumor volume and its capability to produce the vascularized network for further growth of the tumor and remote metastasis. Conclusion. Rg3 inhibited the activation of microtumor vessel formation in vivo besides its apoptosis induction. Rg3 may be used as an adjuvant agent in the clinical HCC treatment regimen.http://dx.doi.org/10.1155/2019/3815786
spellingShingle Shen Hu
Yan Zhu
Xiangyang Xia
Xiaobo Xu
Fen Chen
Xudong Miao
Xinmei Chen
Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
Analytical Cellular Pathology
title Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
title_full Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
title_fullStr Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
title_full_unstemmed Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
title_short Ginsenoside Rg3 Prolongs Survival of the Orthotopic Hepatocellular Carcinoma Model by Inducing Apoptosis and Inhibiting Angiogenesis
title_sort ginsenoside rg3 prolongs survival of the orthotopic hepatocellular carcinoma model by inducing apoptosis and inhibiting angiogenesis
url http://dx.doi.org/10.1155/2019/3815786
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