Significance of COX-2 expression in human renal cell carcinoma cell lines.
Accumulating evidences indicate that cyclooxygenase (COX)-2 plays an important role in tumorigenesis in many human cancers. Yet the relationship between COX-2 and human renal cell carcinoma (RCC) remains unclear. The aim of our study was to evaluate COX-2 expression in human RCC cell lines and its role in tumorigenesis of human RCC. Among the human RCC cell lines (SMKT-R4, OS-RC-2, ACHN) and normal renal cell line RPTEC, COX-2 overexpression was found in OS-RC-2 cells both at mRNA and protein levels. COX-2 sense- and antisense-orientated vectors were constructed and transferred into RCC cells. Significant suppression of cellular proliferation was demonstrated in OS-RC-2 antisense transfectants, whereas promotion was found in SMKT-R4 sense transfectants by colony-forming assay despite the observation that COX-2 specific inhibitor NS398 exhibited similar IC50 among RCC cell lines by MTT assay. In comparison with parent cells and sense transfectants, significant suppression of COX-2 expression and PGE2 production and increase in butyrate-induced apoptosis were observed in OS-RC-2 antisense transfectants by Western blot, ELISA assay and FACS analysis, respectively. Furthermore, tumor growth and angiogenesis of OS-RC-2 antisense transfectants in nude mice was significantly suppressed and the survival time of these mice was significantly prolonged. Our study demonstrates that COX-2 is overexpressed in OS-RC-2 RCC cell line and plays an important role in tumorigenesis of the cells in vivo, which implies that COX-2 may be a therapeutic target for COX-2-expressing RCC, and that suppression of COX-2 expression by antisense-based strategy may have potential utility in treatment of COX-2-expressing RCC.
Chen
Qinzhong
Q
Department of Urology, Hokkaido University Graduate School of Medicine, North-15 West-7, North Ward, Sapporo 060-8638, Japan.
Shinohara
Nobuo
N
Abe
Takashige
T
Watanabe
Takafumi
T
Nonomura
Katsuya
K
Koyanagi
Tomohiko
T
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000378:metabolism; D002455:Cell Division; D045744:Cell Line, Tumor; D002469:Cell Separation; D004396:Coloring Agents / Q000494:pharmacology; D051546:Cyclooxygenase 2; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000096:biosynthesis*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D009578:Nitrobenzenes / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
D002087:Butyrates; D004396:Coloring Agents; D018076:DNA, Complementary; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D013449:Sulfonamides; D013778:Tetrazolium Salts; D013844:Thiazoles; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C022616:thiazolyl blue