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Significance of COX‐2 expression in human renal cell carcinoma cell lines
Author(s) -
Chen Qinzhong,
Shinohara Nobuo,
Abe Takashige,
Watanabe Takafumi,
omura Katsuya,
Koyanagi Tomohiko
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11646
Subject(s) - carcinogenesis , cell culture , cancer research , biology , transfection , sense (electronics) , angiogenesis , cell growth , mtt assay , microbiology and biotechnology , cancer , chemistry , genetics
Abstract 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. © 2003 Wiley‐Liss, Inc.