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Cyclooxygenase isozymes are expressed in human myeloma cells but not involved in anti‐proliferative effect of cyclooxygenase inhibitors
Author(s) -
Ding Jie,
Tsuboi Kazuhito,
Hoshikawa Hiroshi,
Goto Rieko,
Mori Nozomu,
Katsukawa Michiko,
Hiraki Emi,
Yamamoto Shozo,
Abe Masahiro,
Ueda Natsuo
Publication year - 2006
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20175
Subject(s) - cyclooxygenase , isozyme , cell culture , blot , biology , microbiology and biotechnology , arachidonic acid , prostaglandin , enzyme , prostaglandin e2 , cell growth , biochemistry , gene , endocrinology , genetics
Considering possible tumorigenic activity of cyclooxygenase (COX) isozymes in myeloma, we examined expression levels of COX‐1 and ‐2 in seven human myeloma cell lines (ARH‐77, IM‐9, RPMI‐8226, HPC, HS‐Sultan, TSPC‐1, and U‐266). As analyzed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), all the cell lines constitutively expressed COX‐1, while COX‐2 levels markedly varied among different cell lines. Induction of COX‐2 by phorbol ester was observed in RPMI‐8226 and HPC cells. In contrast, COX‐2 was constitutively expressed in ARH‐77 and IM‐9 cells. Moreover, the high expression level of COX‐2 protein in ARH‐77 cells was verified by Western blotting. Intact cells of ARH‐77 converted 14 C‐labeled arachidonic acid to prostaglandin E 2 , F 2α , and D 2 , and this activity was dose‐dependently inhibited by selective COX‐2 inhibitors (SC‐58125 and NS‐398), a non‐selective COX inhibitor (indomethacin), and relatively high concentrations of a selective COX‐1 inhibitor (SC‐560). These COX inhibitors also suppressed the proliferation of ARH‐77 cells, but significant suppression was seen only at 100 µM, a much higher concentration than those sufficient for the COX inhibition. Moreover, proliferation of the myeloma cells lacking COX‐2 was also suppressed by 100 µM of SC‐58125. These results suggested that the anti‐proliferative effect of the COX inhibitors is independent of the inhibition of COX‐2. © 2005 Wiley‐Liss, Inc.