Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-β1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells

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Abstract

Background

Epithelial-mesenchymal transition (EMT) is a vital process in cancer progression and metastasis. Yanggan Jiedu Sanjie (YGJDSJ) is Traditional Chinese Medicine formulation for liver cancer treatment. In the present study, we evaluated the effects of YGJDSJ on TGF-β1-induced EMT in hepatocellular carcinoma Bel-7402 cells.

Methods

Bel-7402 cells were treated with TGF-β1 and YGJDSJ. EMT was identified by morphological changes and expression of marker proteins. Cell morphology was observed under a microscope. Protein expression and phosphorylation was detected by western blotting. Cell migration was measured by the scratch assay. Cell adhesion and invasion was detected by a commercial kit.

Results

YGJDSJ reversed TGF-β1-induced morphological changes, as well as the expression of the EMT markers E-cadherin and N-cadherin in Bel-7402 cells. YGJDSJ also inhibited TGF-β1 up-regulated Smad3 phosphorylation and Snail expression in Bel-7402 cells. Moreover, YGJDSJ inhibited TGF-β1-induced cell adhesion, migration and invasion in Bel-7402 cells.

Conclusions

YGJDSJ inhibited TGF-β1-induced EMT and mediated metastatic potential of Bel-7402 cells, which may be related to down-regulation of Smad3 phosphorylation and Snail expression. The present study provides a new basis for application of this herbal formula for prevention of liver cancer metastasis.

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Most cited references 41

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The diagnosis and treatment of hepatocellular carcinoma.

Justin Hartke, Matthew W. Johnson, Marwan Ghabril (2017)

Hepatocellular carcinoma is a leading cancer worldwide. Its incidence is increasing, and is closely related to advanced liver disease. Cirrhosis represents the greatest risk factor for this malignancy, and is the main indication for screening and surveillance. The diagnosis of hepatocellular carcinoma can frequently, and uniquely, be made on characteristic multiphase contrast based cross-sectional imaging rather than strict need for tissue sampling. Despite advances in medical, locoregional and surgical therapies, hepatocellular carcinoma remains one of the most common causes of cancer-related death globally. In this review, current approaches to management of hepatocellular carcinoma are discussed, which incorporate both tumor and patient factors. The salient considerations in surgical (resection, liver transplantation), locoregional (ablation and embolic therapies) and medical therapies are highlighted.

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Clinical features of hepatocellular carcinoma with extrahepatic metastases.

Toshihiro Suga, Yoshiyasu Karino, Jouji Toyota … (2005)

There are few detailed clinical reports about extrahepatic metastases of hepatocellular carcinoma (HCC). The purpose of the present study was to elucidate the clinical features of extrahepatic metastases of HCC. The clinical records of 482 patients who had been diagnosed as having HCC during the period from January 1995 to March 2001 were retrospectively reviewed. Extrahepatic metastases had been detected in 65 patients. Clinical features of those 65 patients were analyzed. Patients with extrahepatic metastases had more advanced intrahepatic tumors at the first diagnosis of HCC: 73.8% of the patients with extrahepatic metastases had tumors of intrahepatic tumor stage T3 or T4 according to the TNM classification, while only 28.5% of the patients without extrahepatic metastases had tumors of T3 or T4 (P < 0.001). Vessel invasion was also detected at the first diagnosis of HCC more frequently in the patients with extrahepatic metastasis (P < 0.001). The frequent metastatic sites were lung (53.8%), bone (38.5%), and lymph node (33.8%). Other metastatic sites were the adrenal gland, peritoneum, skin, brain and muscle. The median survival time and 1-year survival rate were 7 months (range: 1-59 months) and 24.9%, respectively. Patients with Child-Pugh grade B and C (P = 0.0018) and patients with positive serum alpha-fetoprotein (P = 0.011) had significantly poor prognosis. Extrahepatic metastases of HCC are not rare. The possibility of extrahepatic metastases and the clinical features of extrahepatic metastases should be considered when examining patients with HCC, particularly those with advanced intrahepatic tumors, to enable precise evaluation of the spread of HCC and determination of the appropriate treatment method. (c) 2005 Blackwell Publishing Asia Pty Ltd.

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Structural determinants of Smad function in TGF-β signaling.

Maria Macias, Pau Martín-Malpartida, Joan Massagué (2015)

Smad transcription factors are central to the signal transduction pathway that mediates the numerous effects of the transforming growth factor β (TGF-β) superfamily of cytokines in metazoan embryo development as well as in adult tissue regeneration and homeostasis. Although Smad proteins are conserved, recent genome-sequencing projects have revealed their sequence variation in metazoan evolution, human polymorphisms, and cancer. Structural studies of Smads bound to partner proteins and target DNA provide a framework for understanding the significance of these evolutionary and pathologic sequence variations. We synthesize the extant mutational and structural data to suggest how genetic variation in Smads may affect the structure, regulation, and function of these proteins. We also present a web application that compares Smad sequences and displays Smad protein structures and their disease-associated variants.

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Author and article information

Contributors

Bing Hu:

ORCID: http://orcid.org/0000-0003-0810-6670

beearhu@hotmail.com

Hong-Mei An: lhsoatp@163.com

Xia Yan: gracemihe@163.com

Jia-Lu Zheng: zhengjialu19851206@126.com

Xiao-Wei Huang: 616278620@qq.com

Miao Li: elviraphoenix@hotmail.com

Journal

Journal ID (nlm-ta): BMC Complement Altern Med

Journal ID (iso-abbrev): BMC Complement Altern Med

Title: BMC Complementary and Alternative Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6882

Publication date (Electronic): 15 March 2019

Publication date PMC-release: 15 March 2019

Publication date Collection: 2019

Volume: 19

Electronic Location Identifier: 67

Affiliations

[1 ]ISNI 0000 0001 2372 7462, GRID grid.412540.6, Institute of Traditional Chinese Medicine in Oncology, Department of Oncology, Longhua Hospital, , Shanghai University of Traditional Chinese Medicine, ; Shanghai, 200032 People’s Republic of China

[2 ]ISNI 0000 0001 2372 7462, GRID grid.412540.6, Department of Science & Technology, Longhua Hospital, , Shanghai University of Traditional Chinese Medicine, ; Shanghai, 200032 People’s Republic of China

Author information

Bing Hu http://orcid.org/0000-0003-0810-6670

Article

Publisher ID: 2477

DOI: 10.1186/s12906-019-2477-9

PMC ID: 6420768

PubMed ID: 30876428

SO-VID: 96e576ee-dd86-49f3-a154-9a8f4b1fd4a5

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 May 2018

Date accepted : 10 March 2019

Funding

Funded by: Program from Science & Technology Commission of Shanghai Municipality

Award ID: 09JC1413600 and 16401902500

Award Recipient : Bing Hu

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: hepatocellular carcinoma,epithelial-mesenchymal transition,chinese herbal medicine,metastasis

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: hepatocellular carcinoma, epithelial-mesenchymal transition, chinese herbal medicine, metastasis

Traditional Chinese medicine formulation Yanggan Jiedu Sanjie inhibits TGF-β1-induced epithelial-mesenchymal transition and metastatic potential in human hepatocarcinoma Bel-7402 cells

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Abstract

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Conclusions

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Karger: Oncology

Most cited references 41

The diagnosis and treatment of hepatocellular carcinoma.

Clinical features of hepatocellular carcinoma with extrahepatic metastases.

Structural determinants of Smad function in TGF-β signaling.

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