Antitumoral effect of selective cycloxygenase-2 inhibitor against urological cancer

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INTRODUCTION AND OBJECTIVE: Cytotoxic chemotherapy has shown little or no antitumor activity against renal cell carcinoma (RCC) and has played no role in either an adjuvant or a neoadjuvant support therapy. Immunoterapy is relatively effective against RCC, but the efficacy is not strong. It has been reported that COX-2 inhibitors prevent carcinogenesis of colon cancer and induce apoptosis in colon cancer, esophageal cancer and hung cancer cells. In the present study, we investigated the expression of COX-2 in RCC, and cytotoxic and cytostatic effects of a selective COX-2 inhibitor (ITE-522) on RCCMETHODS: The expression of COX-2 in RCC cell lines (Caki-1, NC65, and ACHN) and normal renal cell line (RPTEC) were examined by reverse transcription polymerase chain reaction. The cytotoxic and cytostatic effects of JTE-522 on the cell lines were assessed by 1-day and 3-day MTT assayRESULTS: The expression of COX-2 was observed in all RCC cell lines examined but not RPTEC. JTE-522 was cytotoxic against Caki-1, NC65, and ACHN cells and inhibited their proliferation, but not RPTEC. These was a synergistic cytotoxisc effect of JTE-522 in combination with 5-fluolouracil, adriamycin, cis-diammine-dichloroplatirum, interfelon-α or tumor necrosis factor-α commonly used against RCC resulted in an additive cytotoxic effect on Caki-1 cellsCONCLUSIONS: The present study has demonstrated that a selective COX-2 inhibitor (JTE-522) has cytotoxic and cytostatic effects on RCC but not normal renal cells, and that synergistic cytotoxicity against RCC was obtained with JTE-522 and anti-Fas monoclonal antibody. These results suggest that the treatment with selective COX-2 inhibitors and immunotherapy may be useful in patient with RCC