5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.
5-Lipoxygenase inhibitors attenuate growth of human renal cell carcinoma and induce apoptosis through arachidonic acid pathway.
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DOI：
10.3892/or.14.1.73
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发表时间：
2005-07
期刊：
影响因子：
4.2
通讯作者：
M. Matsuyama;R. Yoshimura;M. Mitsuhashi;K. Tsuchida;Y. Takemoto;Y. Kawahito;H. Sano;T. Nakatani
中科院分区：
文献类型：
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作者：
M. Matsuyama;R. Yoshimura;M. Mitsuhashi;K. Tsuchida;Y. Takemoto;Y. Kawahito;H. Sano;T. Nakatani
花生四烯酸通过环氧合酶或脂氧合酶（LOX）途径的代谢被认为在肿瘤促进中发挥重要作用。我们研究了 5- 和 12-LOX 在肾细胞癌 (RCC) 中的表达，以及它们的抑制剂对 2 个 RCC 细胞系（Caki-1 和 A498）中细胞增殖的影响。通过免疫组织化学和RT-PCR检测5-和12-LOX的表达。采用MTT法检测LOX抑制剂对RCC细胞生长的影响，并采用Hoechst染色法测定LOX抑制剂是否诱导细胞凋亡。虽然在 NK 组织中检测到轻微的 5- 和 12-LOX 表达水平，但在 RCC 组织中检测到显着的 5- 和 12-LOX 表达水平。 5-LOX 抑制剂以浓度和时间依赖性方式导致肾细胞癌细胞显着减少。 5-LOX抑制剂的作用强于12-LOX抑制剂。此外，5-LOX抑制剂通过细胞凋亡导致肾细胞癌细胞显着减少。 LOX，尤其是 5-LOX，在 RCC 中被诱导，结果表明 5-LOX 抑制剂可能介导针对 RCC 细胞的有效抗增殖作用。因此，5-LOX可能成为治疗RCC的新靶点。
The metabolism of arachidonic acid by either the cyclooxygenase or lipoxygenase (LOX) pathway is believed to play an important role in tumor promotion. We investigated the expression of 5- and 12-LOX in renal cell carcinoma (RCC), as well as the effects of their inhibitors on cell proliferation in 2 RCC cell lines (Caki-1 and A498). Expression of 5- and 12-LOX was detected by immunohistochemistry and RT-PCR. Effects of LOX inhibitors on RCC cell growth were examined by MTT assay, and Hoechst staining was used to determine whether or not the LOX inhibitors induce apoptosis. While 5- and 12-LOX expression levels were slightly detected in NK tissues, marked expressions of 5- and 12-LOX were detected in RCC tissues. 5-LOX inhibitors caused marked reduction of RCC cells in a concentration- and time-dependent manner. The effect of the 5-LOX inhibitor was stronger than the 12-LOX inhibitor. Furthermore, the 5-LOX inhibitor caused a marked reduction of RCC cells through apoptosis. LOX, especially 5-LOX, is induced in RCC, and the results suggest that the 5-LOX inhibitor may mediate potent anti-proliferative effects against RCC cells. Thus, 5-LOX may become a new target in treatment of RCC.