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

BMC Cancer

Research Article

Qi Li¹  Xuan Liu¹  Qiong Wu¹  Ningning Liu¹  Ning Zhou¹  Haili Jiang¹  Ni Chai¹ 

[1] Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, No. 528 Zhangheng Road, 201203, Shanghai, P. R. China;

关键词: Helicobacter pylori;    Gastric cancer;    Vascular endothelial growth factor;    Cyclooxygenase 2;    Wnt/beta-catenin;    Angiogenesis;   

DOI  :  10.1186/s12885-016-2351-9

 received in 2015-04-11, accepted in 2016-05-11,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHelicobacter 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.MethodsTo 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.ResultsH. 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© Liu et al. 2016