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半胱氨酰白三烯 1 型受体是预防和治疗人类泌尿系统癌症的有效靶点。

Cysteinyl-leukotriene1 receptor is a potent target for the prevention and treatment of human urological cancer.

机构信息

Department of Urology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.

出版信息

Mol Med Rep. 2010 Mar-Apr;3(2):245-51. doi: 10.3892/mmr_00000247.

Abstract

Leukotrienes (LTs) are biologically active fatty acids derived from the oxidative metabolism of arachidonic acid through the 5-lipoxygenase pathway. LTs work to contract airway smooth muscle, increase vascular permeability and mucus secretions, and attract and activate inflammatory cells in the airways of patients with asthma. Recently, it was reported that the LTD4 receptor (cysteinylLT1 receptor; CysLT1R) plays an important role in carcinogenesis. In this study, CysLT1R expression was examined in human urological cancer cell lines (renal cell carcinoma, bladder cancer, prostate cancer and testicular cancer) using immunohistochemistry and RT-PCR. The effect of CysLT1R antagonist on these cells was also examined using the MTT assay, Hoechst staining and flow cytometry. CysLT1R expression was significantly more extensive and intense in the malignant tissues than in normal tissues. Furthermore, CysLT1R antagonist induced a reduction in malignant cell viability through early apoptosis. These results demonstrate that CysLT1R expressed in urological cancer may play a crucial role in carcinogenesis. CysLT1R may therefore be a novel target in the treatment of urological cancer.

摘要

白三烯(LTs)是通过 5-脂氧合酶途径从花生四烯酸的氧化代谢中衍生而来的生物活性脂肪酸。LTs 作用于收缩气道平滑肌,增加血管通透性和黏液分泌,并吸引和激活哮喘患者气道中的炎症细胞。最近有报道称,LTD4 受体(半胱氨酰白三烯 1 型受体;CysLT1R)在癌症发生中发挥重要作用。在这项研究中,使用免疫组织化学和 RT-PCR 检查了人类尿路上皮癌细胞系(肾细胞癌、膀胱癌、前列腺癌和睾丸癌)中的 CysLT1R 表达。还使用 MTT 测定、Hoechst 染色和流式细胞术检查了 CysLT1R 拮抗剂对这些细胞的影响。CysLT1R 在恶性组织中的表达明显比在正常组织中更广泛和强烈。此外,CysLT1R 拮抗剂通过早期凋亡诱导恶性细胞活力降低。这些结果表明,尿路上皮癌中表达的 CysLT1R 可能在癌症发生中发挥关键作用。因此,CysLT1R 可能成为治疗尿路上皮癌的新靶点。

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