위선암종의 발생과 진행에 따른 COX-2 및 PGE2의 역할

Abstract

Objective : COX-2-derived PGE₂ has been implicated in the development of various cancers. PGE₂ promotes cancer proliferation by modulating proliferation, apoptosis, and angiogenesis. It is a downstream product of COX and is biochemically inactivated by prostaglandin dehydrogenase (PGDH). Selective targeting of PGE₂ or receptors might be useful with respect to cancer. Substantial interest is focused on microsomal prostaglandin E synthase (mPGES)-1, which is upregulated in numerous human cancers. The aim of this study was to investigate the role of COX-2 and PGE₂ in cancer progression and metastasis in the stomach. Methods : Expression of COX-2, mPGES and 15-PGDH were examined by immunohistochemistry in a series of 48 cases of adenocarcinoma (advanced gastric carcinoma: 24 cases, early gastric carcinoma: 24 cases) and 12 cases of adenoma of stomach. Their clinicopathologic correlation was statistically evaluated. Results : COX-2 expression was correlated with cancer progression and lymph node metastasis. mPGES expression was correlated with lymph node metastasis. Increament of mPGES and decrement of PGDH were related to the progression of cancer. Strong immunoreactivity for COX-2 had statistically significant reverse correlation with the 15-PGDH expression. Conclusion : The author assumed that the immunohistochemical expression of COX-2, mPGES, or PGDH had a significant correlation with PGE₂. Therefore, modulation of mPGES or PGDH could help to prevent or treat the progression of the gastric adenocarcinoma without serious side effects of the COX-2 blockers.