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Journal of Environmental Pathology, Toxicology and Oncology
Импакт фактор: 1.241 5-летний Импакт фактор: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Печать: 0731-8898
ISSN Онлайн: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v21.i2.100
12 pages

In Vitro Evidence of the Role of COX-2 in Attenuating Gastric Inflammation and Promoting Gastric Carcinogenesis

Ki-Baik Hahm
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
Ho-Yeong Lim
Departments of Oncology, Ajou University School of Medicine, Suwon, Korea
Seonghyang Sohn
Departments of Dermatology, Ajou University School of Medicine, Suwon, Korea
Hyuk-Jae Kwon
Departments of Dermatology, Ajou University School of Medicine, Suwon, Korea
Ki-Myung Lee
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea
Jeong-Sang Lee
College of Pharmacology, Seoul National University, Seoul, Korea
Young-Joon Surh
Seoul National University, South Korea
Young-Bae Kim
Departments of Pathology,5 Ajou University School of Medicine, Suwon, Korea
Hee-Jae Joo
Departments of Pathology,5 Ajou University School of Medicine, Suwon, Korea
Won-Seok Kim
School of Engineering The Robert Gordon University Schoolhill, Aberdeen, AB10 1FR, UK
Seung-Won Cho
Departments of Gastroenterology, Ajou University School of Medicine, Suwon, Korea

Краткое описание

Although gastric adenocarcinoma is one of the most common malignancies in the world, little is known about its exact molecular processes in development and progression. Recent studies suggest that COX-2 is important in carcinogenesis of gastrointestinal cancers, and is especially involved in carcinogenesis in a mouse model of familial adenomatosis polyposis. To understand the role of COX-2 in gastric carcinogenesis and Helicobacter pylori-associated gastritis, we measured COX-2 expression in 170 human gastric carcinoma tissues by immunohistochemical analysis and compared the expression of COX-2 in paired tissues obtained from normal-looking and cancer-bearing mucosa. Further evidence of the involvement of COX-2 in gastritis and gastric carcinogenesis was obtained by establishing stable cell lines overexpressing COX-2. After subcloning of COX-2 into pCB7 mammalian expression vector, two stable cell lines named MKN-28-COX-2 and MKN-45-COX-2 were generated by transfection of COX-2 cDNA. To understand the effect of COX-2 on gastritis, we performed an electrophoretic mobility shift assay of NF-kB (inflammation-associated transcription factor), and measured malondialdehyde levels and chemiluminescence activities in both mock-transfected MKN and MKN-COX-2 cells after stimulation of H. pylori (1 x 106 CFU/mL) and neutrophils (102 cells/mL). A marked attenuation ofNF-kB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-b treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-b through decreasing TGF-b RII expression and increased cell invasiveness. In conclusion, COX-2 expression seems to be induced to attenuate the degree of atrophic gastritis, the initial event in gastric carcinogenesis, and promote gastric carcinogenesis.


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