Effects of NSAIDs on proliferation of gastric cancer cells in vitro: possible implication of cyclooxygenase-2 in cancer development.
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.
Sawaoka
H
H
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Kawano
S
S
Tsuji
S
S
Tsujii
M
M
Murata
H
H
Hori
M
M
D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin