Matsuyama Masahide, Yoshimura Rikio, Tsuchida Kenji, Takemoto Yoshiaki, Segawa Yoshihiro, Shinnka Toshiaki, Kawahito Yutaka, Sano Hajime, Nakatani Tatsuya
Department of Urology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan.
Int J Mol Med. 2004 May;13(5):665-8.
Recent studies have demonstrated that lipoxygenase (LOX) inhibitor induces growth arrest of cancer cells through apoptosis. In this study, we examined the effects of LOX inhibitors on cell proliferation in renal cell carcinoma (RCC), bladder tumor (BT), and prostate cancer (PC) cell lines. We investigated the inhibitory effect of LOX inhibitors, 5-, 12- and non-specific LOX inhibitor on RCC, BT and PC-derived cell lines using MTT assay and Hoechst staining. All LOX inhibitors induced the reduction of cell viability with the half-maximal concentration of growth inhibition of RCC, BT, and PC cell lines. Furthermore, counting cells at days 1, 2 and 3, clearly showed marked inhibition of cell proliferation by treatment with non-specific and 5-LOX inhibitor. All LOX inhibitors stopped the growth of all RCC, BT and PC cells. The effect of non-specific LOX inhibitor was strongest. The effect of 5-LOX inhibitor was stronger than 12-LOX inhibitor. All LOX inhibitors caused marked inhibition of urological cancer cells through apoptosis. LOX inhibitor may mediate potent antiproliferative effects against RCC, BT and PC cells through differentiation. Thus, LOX inhibitor, especially 5-LOX inhibitor may become a new target in treatment of urological cancers.
最近的研究表明,脂氧合酶(LOX)抑制剂可通过诱导癌细胞凋亡来使其生长停滞。在本研究中,我们检测了LOX抑制剂对肾细胞癌(RCC)、膀胱肿瘤(BT)和前列腺癌(PC)细胞系中细胞增殖的影响。我们使用MTT法和Hoechst染色研究了5-LOX、12-LOX抑制剂及非特异性LOX抑制剂对RCC、BT和PC来源的细胞系的抑制作用。所有LOX抑制剂均能使RCC、BT和PC细胞系的细胞活力降低,且半数最大生长抑制浓度出现下降。此外,在第1、2和3天对细胞进行计数,结果清楚地显示,非特异性LOX抑制剂和5-LOX抑制剂处理可显著抑制细胞增殖。所有LOX抑制剂均能使所有RCC、BT和PC细胞停止生长。非特异性LOX抑制剂的作用最强。5-LOX抑制剂的作用强于12-LOX抑制剂。所有LOX抑制剂均可通过诱导凋亡显著抑制泌尿系统癌细胞。LOX抑制剂可能通过分化介导对RCC、BT和PC细胞的强大抗增殖作用。因此,LOX抑制剂,尤其是5-LOX抑制剂可能成为治疗泌尿系统癌症的新靶点。