Helicobacter pylori promotes VEGF expression via the p38 MAPK‑mediated COX‑2‑PGE2 pathway in MKN45 cells

Liu,Ningning; Wu,Qiong; Wang,Yan; Sui,Hua; Liu,Xuan; Zhou,Ning; Zhou,Lihong; Wang,Yifei; Ye,Naijing; Fu,Xiaoling; Yu,Nikitin  Alexander; Li,Qi

doi:10.3892/mmr.2014.2458

Helicobacter pylori promotes VEGF expression via the p38 MAPK‑mediated COX‑2‑PGE2 pathway in MKN45 cells

Authors:
- Ningning Liu
- Qiong Wu
- Yan Wang
- Hua Sui
- Xuan Liu
- Ning Zhou
- Lihong Zhou
- Yifei Wang
- Naijing Ye
- Xiaoling Fu
- Nikitin Alexander Yu
- Qi Li
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Affiliations: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Interventional Cancer Institute of Integrative Medicine and Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853‑6401, USA
Published online on: August 6, 2014 https://doi.org/10.3892/mmr.2014.2458
Pages: 2123-2129

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Abstract

Helicobacter pylori has been suggested to be the major cause of gastric malignancy. However, the pathogenesis and molecular mechanisms of gastric tumorigenesis induced by H. pylori infection are yet to be elucidated. In the present study, the expression levels of vascular endothelial growth factor (VEGF), which has been suggested to promote angiogenesis in gastric cancer, were found to be elevated in H. pylori‑infected MKN45 cells. Furthermore, it was demonstrated that the expression of VEGF was modulated by the p38 mitogen‑activated protein kinases (MAPK) pathway via regulation of the cyclooxygenase (COX)‑2 pathway. It was also found that prostaglandin E2 (PGE2) and its receptor EP2/EP4 may mediate the upregulation of VEGF in gastric cells exposed to H. pylori. In combination, these results suggest that VEGF expression is regulated by the p38 MAPK COX‑2-PGE2‑EP2/EP4 pathway in gastric cancer cells induced by H. pylori. This provides a theoretical basis for the investigation of the pathogenesis of H. pylori‑induced gastric cancer.

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