COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer in vitro
COX-2 inhibition demonstrates potent anti-proliferative effects on bladder cancer in vitro
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DOI：
10.1016/j.jss.2004.03.005
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发表时间：
2004-06-15
影响因子：
2.2
通讯作者：
Kandzari, S
中科院分区：
文献类型：
--
作者：
Mohseni, H;Zaslau, S;Kandzari, S
目的.本工作的目的是确定罗非昔布和特异性考克斯1和考克斯2抑制剂在体外对细胞生长、凋亡和坏死活性的影响。罗非昔布（万络）是一种选择性抑制环氧合酶-2（考克斯-2）的非甾体抗炎药（NSAID）。诱导型同种型。考克斯-2在许多胃肠道和泌尿生殖道肿瘤中过表达。我们假设用考克斯-1和考克斯-2抑制剂进行体外治疗将通过凋亡途径显著降低膀胱癌细胞的细胞增殖。使用标准技术使两种人膀胱癌细胞系在培养物中生长，并用剂量范围从125 μ g/孔连续稀释至8.0 μ g/孔的罗非考昔处理。儿茶素（考克斯1抑制剂）和NS 398（考克斯2抑制剂）以50和100 μ m的剂量使用。在24和72 h通过MTT法测定细胞活力。通过Annexin V FITC测定评价细胞凋亡。统计学分析采用方差分析。与未处理的对照相比，罗非考昔、儿茶素和NS 398均表现出显著的细胞生长抑制。在T24细胞和TCC 40细胞中，在所有测试的药物中均观察到凋亡活性的显著变化。选择性考克斯-2抑制，使用耐受性良好和市售的罗非昔布（VIOXX）和特异性考克斯1和2抑制剂，通过凋亡机制减少体外人膀胱癌的生长。进一步的体内和人体研究是必要的，以评估这种药物在膀胱癌患者中的安全性和临床效用。(C)2004爱思唯尔公司All rights reserved.
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 mug/well serially diluted down to 8.0 mug/well. Catechin (COX 1 inhibitor) and NS398 (COX 2 inhibitor) were used at doses of 50 and 100 mum. 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. (C) 2004 Elsevier Inc. All rights reserved.