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.
MeSH Terms
Cell Line, Tumor
Cyclooxygenase 2/chemistry,genetics,metabolism
Dinoprostone/metabolism
HEK293 Cells
Helicobacter pylori/pathogenicity
Humans
Imidazoles/pharmacology
Nitrobenzenes/pharmacology
Pyridines/pharmacology
RNA Interference
RNA, Small Interfering/metabolism
Receptors, Prostaglandin E, EP2 Subtype/metabolism
Receptors, Prostaglandin E, EP4 Subtype/metabolism
Sulfonamides/pharmacology
Up-Regulation/drug effects
Vascular Endothelial Growth Factor A/metabolism
p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism
Chemicals
Imidazoles
Nitrobenzenes
Pyridines
RNA, Small Interfering
Receptors, Prostaglandin E, EP2 Subtype
Receptors, Prostaglandin E, EP4 Subtype
Sulfonamides
Vascular Endothelial Growth Factor A
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
Cyclooxygenase 2
p38 Mitogen-Activated Protein Kinases
Dinoprostone
SB 203580
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Liu Ningning
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Wu Qiong
Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Wang Yan
Interventional Cancer Institute of Integrative Medicine and Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Sui Hua
Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Liu Xuan
Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Zhou Ning
Department of Medical Oncology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Zhou Lihong
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Wang Yifei
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Ye Naijing
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Fu Xiaoling
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
Yu Nikitin Alexander
Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853‑6401, USA.
Li Qi
Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China.
