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The Target of 5-Lipoxygenase is a Novel Strategy over Human Urological Tumors than the Target of Cyclooxygenase-2

机译:5-脂氧合酶的靶标是比环氧合酶-2靶标治疗人类泌尿外科肿瘤的新策略

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The metabolism of arachidonic acid by either the cyclooxygenase (COX) or lipoxygenase (LOX) pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including cancer. It is now considered that they play important roles in tumor promotion, progression, and metastasis, also, the involvement of COX and LOX expression and function in tumor growth and metastasis has been reported in human tumor cell lines. In this study, we examined the expression of COX and LOX in human urological tumors (renal cell carcinoma, bladder tumor, prostate cancer, testicular cancer) by immunohistochemistry and RT-PCR, and we also examined the effects of COX and LOX (5- and 12-LOX) inhibitors in those cells by MTT assay, hoechest staining, and flow cytometry. COX-2, 5-LOX and 12-LOX expressions were significantly more extensive and intense in malignant tissues than in normal tissues. Furthermore, 5-LOX inhibitor induced the reduction of malignant cell viability through early apoptosis. These results demonstrated COX-2 and LOX were induced in urological tumors, and 5-LOX inhibitor may mediate potent antiproliferative effects against urological tumors cells. Thus, 5-LOX may become a new target in the treatment of urological tumors.
机译:花生四烯酸通过环氧合酶(COX)或脂氧合酶(LOX)途径的代谢产生类花生酸,这与多种人类疾病(包括癌症)的发病机制有关。现在认为它们在肿瘤的促进,进展和转移中起着重要的作用,而且在人类肿瘤细胞系中已经报道了COX和LOX的表达和功能参与肿瘤的生长和转移。在这项研究中,我们通过免疫组织化学和RT-PCR研究了COX和LOX在人泌尿外科肿瘤(肾细胞癌,膀胱肿瘤,前列腺癌,睾丸癌)中的表达,并研究了COX和LOX的作用(5- MTT分析,hoechest染色和流式细胞仪检测这些细胞中的12和LOX抑制剂)。与正常组织相比,恶性组织中的COX-2、5-LOX和12-LOX表达明显更广泛和更强烈。此外,5-LOX抑制剂通过早期凋亡诱导了恶性细胞活力的降低。这些结果证明COX-2和LOX在泌尿外科肿瘤中被诱导,而5-LOX抑制剂可能介导针对泌尿外科肿瘤细胞的有效抗增殖作用。因此,5-LOX可能成为泌尿外科肿瘤治疗的新目标。

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