Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibito...

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Main Authors: Yi Zhang, Gan-Lin Zhang, Xu Sun, Ke-Xin Cao, Ya-Wen Shang, Mu-Xin Gong, Cong Ma, Nan Nan, Jin-Ping Li, Ming-Wei Yu, Guo-Wang Yang, Xiao-Min Wang
Format: Article
Language:English
Published: MDPI AG 2017-05-01
Series:Molecules
Subjects:
Online Access:http://www.mdpi.com/1420-3049/22/5/787
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author Yi Zhang
Gan-Lin Zhang
Xu Sun
Ke-Xin Cao
Ya-Wen Shang
Mu-Xin Gong
Cong Ma
Nan Nan
Jin-Ping Li
Ming-Wei Yu
Guo-Wang Yang
Xiao-Min Wang
author_facet Yi Zhang
Gan-Lin Zhang
Xu Sun
Ke-Xin Cao
Ya-Wen Shang
Mu-Xin Gong
Cong Ma
Nan Nan
Jin-Ping Li
Ming-Wei Yu
Guo-Wang Yang
Xiao-Min Wang
author_sort Yi Zhang
collection DOAJ
description Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.
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spelling doaj.art-858eea67a41846ec89097bce496884612022-12-22T03:31:49ZengMDPI AGMolecules1420-30492017-05-0122578710.3390/molecules22050787molecules22050787Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT PathwaysYi Zhang0Gan-Lin Zhang1Xu Sun2Ke-Xin Cao3Ya-Wen Shang4Mu-Xin Gong5Cong Ma6Nan Nan7Jin-Ping Li8Ming-Wei Yu9Guo-Wang Yang10Xiao-Min Wang11Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaDepartment of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, ChinaGubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.http://www.mdpi.com/1420-3049/22/5/787Gubenyiliu IIbreast tumorheparanasegrowth factorsERK and AKT pathways
spellingShingle Yi Zhang
Gan-Lin Zhang
Xu Sun
Ke-Xin Cao
Ya-Wen Shang
Mu-Xin Gong
Cong Ma
Nan Nan
Jin-Ping Li
Ming-Wei Yu
Guo-Wang Yang
Xiao-Min Wang
Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
Molecules
Gubenyiliu II
breast tumor
heparanase
growth factors
ERK and AKT pathways
title Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
title_full Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
title_fullStr Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
title_full_unstemmed Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
title_short Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways
title_sort gubenyiliu ii inhibits breast tumor growth and metastasis associated with decreased heparanase expression and phosphorylation of erk and akt pathways
topic Gubenyiliu II
breast tumor
heparanase
growth factors
ERK and AKT pathways
url http://www.mdpi.com/1420-3049/22/5/787
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