S-Space Graduate School of Convergence Science and Technology (융합과학기술대학원) Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과) Journal Papers (저널논문_분자의학 및 바이오제약학과)
In vitro evidence of the role of COX-2 in attenuating gastric inflammation and promoting gastric carcinogenesis
- Hahm, K.-B.; Lim, H.-Y.; Sohn, S.; Kwon, H.-J.; Lee, K.-M.; Lee, J.-S.; Surh, Young-Joon; Kim, Y.-B.; Joo, H.-J.; Kim, W.-S.; Cho, S.-W.
- Issue Date
- Journal of Environmental Pathology, Toxicology and Oncology, Vol.21 No.2, pp.165-176
- Apoptosis; COX-2; Gastric carcinogenesis; Helicobacter pylori; MKN-28; MKN-45; Proliferation
- 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-κB (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 × 106 CFU/mL) and neutrophils (102 cells/mL). A marked attenuation of NF-κB bindings and generation of free radicals was observed in COX-2 overexpressed cells. Another set of experiments, including the growth inhibition by TGF-β treatment, Matrigel invasion assay, and apoptosis assay, was done. COX-2 showed the advantage of the escape from the growth inhibition by TGF-β through decreasing TGF-β 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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