Effects of NSAIDs on proliferation of gastric cancer cells in vitro:: Possible implication of cyclooxygenase-2 in cancer development
Effects of NSAIDs on proliferation of gastric cancer cells in vitro:: Possible implication of cyclooxygenase-2 in cancer development
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DOI：
10.1097/00004836-199800001-00009
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发表时间：
1998-01-01
影响因子：
2.9
通讯作者：
Hori, M
中科院分区：
文献类型：
--
作者：
Sawaoka, H;Kawano, S;Hori, M
环氧合酶-2（考克斯-2）在胃癌发生发展中的作用尚不清楚。我们研究了非甾体类抗炎药（NSAID），这是特异性和非特异性的考克斯-2抑制剂，对胃癌细胞株KATO III，MKN 28和MKN 45的增殖的影响。通过Western分析检测这些细胞系中考克斯-2的蛋白水平，通过北方分析检测考克斯-1/2的mRNA水平。这些细胞系表达相当水平的考克斯-1 mRNA。但考克斯-2在不同细胞系中的mRNA和蛋白表达存在差异。MKN 45表达的考克斯-2 mRNA和蛋白水平高于KATO III和MKN 28。我们还研究了NS-398和吲哚美辛，特异性和非特异性的考克斯-2抑制剂，对这些细胞系的细胞数量和[H-3]胸苷摄取的增加的影响。NS-398和消炎痛抑制过表达考克斯-2的MKN 45细胞的增殖，尽管它们对表达较低水平的考克斯-2的KATOIII和MKN 28的增殖影响很小。这些结果与考克斯-2在某些胃癌中表达并与其细胞增殖有关的假设一致。提示考克斯-2在胃癌细胞的发生发展中起重要作用。此外，NSAID可对过表达考克斯-2的胃腺癌发挥抗增殖活性。
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 [H-3]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.