Antitumoral effect of selective cycloxygenase-2 inhibitor against urological cancer

选择性环加氧酶2抑制剂对泌尿系统肿瘤的抗肿瘤作用

• 批准号: 13671664
• 负责人: NOMOTO Takeshi
• 金额: $ 0.7万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671664/
• 关键词: selective cyclooxygenase-2 inhibitor; renal cell carcinoma; anti-Fas monoclonal antibody; JTE-522; COX-2

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

导言和目的：细胞毒性化疗对肾细胞癌（RCC）的抗肿瘤活性很小或没有，并且在辅助或新辅助支持治疗中没有发挥作用。免疫治疗对肾癌有较好的疗效，但疗效不强。已有研究表明，考克斯-2抑制剂可预防结肠癌的发生，并诱导结肠癌、食管癌和肺癌细胞凋亡。本研究探讨了考克斯-2在肾细胞癌中的表达及选择性考克斯-2抑制剂ITE-522对肾细胞癌的细胞毒作用和细胞生长抑制作用。方法：采用逆转录聚合酶链反应（RT-PCR）检测考克斯-2在肾细胞癌细胞系（Caki-1、NC 65和ACHN）和正常肾细胞系（RPTEC）中的表达。结果：肾癌细胞株均表达考克斯-2，而RPTEC细胞株无COX-2表达。JTE-522对Caki-1、NC 65和ACHN细胞具有细胞毒性，并抑制其增殖，但对RPTEC无抑制作用。JTE-522与5-氟尿嘧啶、阿霉素、顺铂、Interfelon-α或肿瘤坏死因子-α联合应用对Caki-1细胞有协同的细胞毒作用。目前的研究表明，选择性考克斯-2抑制剂（JTE-522）对RCC细胞具有细胞毒性和细胞生长抑制作用，但对正常肾细胞无作用，JTE-522与抗Fas单克隆抗体对肾癌细胞有协同杀伤作用。提示选择性考克斯-2抑制剂联合免疫治疗对肾细胞癌有一定的疗效

项目成果

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Mizutani Y, et al.: "Synergistic cytotoxicity and apoptosis of JTE-522, a selective cyclooxygenase-2 inhibitor, and 5-fluorouracil against bladder cancer"Journal of Urology. 168・6. 26500-2654 (2003)

Mizutani Y等人：“选择性环氧合酶2抑制剂JTE-522和5-氟尿嘧啶对膀胱癌的协同细胞毒性和细胞凋亡”《泌尿学杂志》168・6（2003）。