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PMID: 27198692 Published · epublish English Journal Article

Helicobacter pylori promotes angiogenesis depending on Wnt/beta-catenin-mediated vascular endothelial growth factor via the cyclooxygenase-2 pathway in gastric cancer.

BMC cancer ·Vol. 16 ·2016-00-19 ·Pages 321

Liu N, Zhou N, Chai N, Liu X, Jiang H, Wu Q, Li Q

Abstract

Helicobacter pylori is an important pathogenic factor in gastric carcinogenesis. Angiogenesis (i.e., the growth of new blood vessels) is closely associated with the incidence and development of gastric cancer. Our previous study found that COX-2 stimulates gastric cancer cells to induce expression of the angiogenic growth factor VEGF through an unknown mechanism. Therefore, the aim of this study was to clarify the role of angiogenesis in H. pylori-induced gastric cancer development. To clarify the relationship between H. pylori infection and angiogenesis, we first investigated H. pylori colonization, COX-2, VEGF, beta-catenin expression, and microvessel density (MVD) in gastric cancer tissues from 106 patients. In addition, COX-2, phospho-beta-catenin, and beta-catenin expression were measured by western blotting, and VEGF expression was measured by ELISA in H. pylori-infected SGC7901 and MKN45 human gastric cancer cells. H. pylori colonization occurred in 36.8 % of gastric carcinoma samples. Furthermore, COX-2, beta-catenin, and VEGF expression, and MVD were significantly higher in H. pylori-positive gastric cancer tissues than in H. pylori-negative gastric cancer tissues (P < 0.01). H. pylori infection was not related to sex or age in gastric cancer patients, but correlated with the depth of tumor invasion, lymph node metastasis, and tumor-node-metastasis stage (P < 0.05) and correlated with the COX-2 expression and beta-catenin expression(P < 0.01). Further cell experiments confirmed that H. pylori infection upregulated VEGF in vitro. Further analysis revealed that H. pylori-induced VEGF expression was mediated by COX-2 via activation of the Wnt/beta-catenin pathway. The COX-2/Wnt/beta-catenin/VEGF pathway plays an important role in H. pylori-associated gastric cancer development. The COX-2/Wnt/beta-catenin pathway is therefore a novel therapeutic target for H. pylori-associated gastric cancers.

Keywords
Angiogenesis Cyclooxygenase 2 Gastric cancer Helicobacter pylori Vascular endothelial growth factor Wnt/beta-catenin
MeSH Terms
Cell Line, Tumor Cyclooxygenase 2/metabolism Gene Expression Gene Expression Regulation, Neoplastic Helicobacter Infections/metabolism,microbiology Helicobacter pylori/physiology Humans Neovascularization, Pathologic/microbiology Stomach Neoplasms/blood supply,metabolism,microbiology Up-Regulation Vascular Endothelial Growth Factor A/physiology Wnt Signaling Pathway beta Catenin/metabolism
Chemicals
CTNNB1 protein, human VEGFA protein, human Vascular Endothelial Growth Factor A beta Catenin Cyclooxygenase 2 PTGS2 protein, human
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Liu Ningning
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Zhou Ning
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Chai Ni
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Liu Xuan
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Jiang Haili
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Wu Qiong
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China.
Li Qi
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, Shanghai, 201203, P. R. China. Lzwf@hotmail.com.
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Article Info
Journal
BMC cancer
Abbr.
BMC Cancer
ISSN
1471-2407
DOI
10.1186/s12885-016-2351-9
Email
lzwf@hotmail.com
Published
2016-00-19
Epub
2016-00-19
Pages
321
Language
English
Region
England
NLM ID
100967800
PMCID
PMC4873996
Subset
IM
External Links
PubMed source DOI: 10.1186/s12885-016-2351-9 PMC Full Text View journal details
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