Sawaoka H, Kawano S, Tsuji S, Tsujii M, Murata H, Hori M
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
J Clin Gastroenterol. 1998;27 Suppl 1:S47-52. doi: 10.1097/00004836-199800001-00009.
The roles of cyclooxygenase-2 (COX-2) in the development of gastric cancer are unknown. We investigated the effects of nonsteroidal antiinflammatory drugs (NSAIDs), which are specific and nonspecific inhibitors of COX-2, on proliferation of the gastric cancer cell lines KATOIII, MKN28, and MKN45. The protein level of COX-2 was examined in these cell lines by Western analysis, and mRNA levels of COX-1/2 by Northern analysis. These cell lines expressed comparable levels of COX-1 mRNA. However, mRNA and protein expression of COX-2 in these cell lines was different. MKN45 expressed higher levels of COX-2 mRNA and protein than KATOIII and MKN28. We also examined the effects of NS-398 and indomethacin, specific and nonspecific inhibitors of COX-2, on the increase in cell number and [3H]thymidine uptake of these cell lines. NS-398 and indomethacin suppressed proliferation of MKN45 cells that overexpressed COX-2, although they exerted minimal effects on proliferation of KATOIII and MKN28, which expressed lower levels of COX-2. These results are consistent with the hypothesis that COX-2 is expressed in certain groups of gastric cancers and is related to their cell proliferation. It was proposed that COX-2 plays an important role in development of gastric cancer cells. Furthermore, NSAIDs may exert antiproliferative activity against gastric adenocarcinomas that overexpress COX-2.
环氧化酶-2（COX-2）在胃癌发生过程中的作用尚不清楚。我们研究了作为COX-2特异性和非特异性抑制剂的非甾体抗炎药（NSAIDs）对胃癌细胞系KATOIII、MKN28和MKN45增殖的影响。通过蛋白质免疫印迹分析检测这些细胞系中COX-2的蛋白水平，通过Northern印迹分析检测COX-1/2的mRNA水平。这些细胞系中COX-1 mRNA的表达水平相当。然而，这些细胞系中COX-2的mRNA和蛋白表达存在差异。MKN45表达的COX-2 mRNA和蛋白水平高于KATOIII和MKN28。我们还检测了COX-2特异性抑制剂NS-398和非特异性抑制剂吲哚美辛对这些细胞系细胞数量增加和[3H]胸腺嘧啶核苷摄取的影响。NS-398和吲哚美辛抑制了过表达COX-2的MKN45细胞的增殖，尽管它们对表达较低水平COX-2的KATOIII和MKN28细胞的增殖影响极小。这些结果与以下假设一致，即COX-2在某些胃癌组中表达并与其细胞增殖有关。有人提出COX-2在胃癌细胞的发生中起重要作用。此外，NSAIDs可能对过表达COX-2的胃腺癌发挥抗增殖活性。
