COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer in vitro

PURPOSE: The purpose of this work was to determine the in vitro effect of Rofecoxib and specific COX 1 and COX 2 inhibitors in regards to cell growth and apoptotic and necrotic activity. INTRODUCTION AND OBJECTIVE: Rofecoxib (Vioxx) is a nonsteroidal anti-inflammatory agent (NSAID) that selectively inhibits cyclooxygenase-2 (COX-2). The inducible isoform of COX-2 is overexpressed in many gastrointestinal and genitourinary tract tumors. We hypothesized that in vitro treatment with both COX-1 and COX-2 inhibitors would significantly reduce cellular proliferation of bladder cancer cells by apoptotic pathways. MATERIALS AND METHODS: Two human bladder cancer cell lines were grown in culture using standard techniques and treated with Rofecoxib at doses ranging from 125 microg/well serially diluted down to 8.0 microg/well. Catechin (COX 1 inhibitor) and NS398 (COX 2 inhibitor) were used at doses of 50 and 100 microM. Cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated by the Annexin V FITC Assay. Statistical analysis was performed by ANOVA. RESULTS: Rofecoxib, Catechin, and NS398 all exhibited significant inhibition of cell growth when compared to the nontreated controls. Significant changes in apoptotic activity were observed in all agents tested in both the T24 and the TCCSUP cells. CONCLUSIONS: Selective COX-2 inhibition, using the well-tolerated and commercially available Rofecoxib (VIOXX) and specific COX 1 and 2 inhibitors, reduced the growth of human bladder cancer in vitro by apoptotic mechanisms. Further in vivo and human studies are warranted to evaluate the safety and clinical utility of this agent in patients with bladder cancer.