Yoshimura Rikio, Matsuyama Masahide, Tsuchida Kenji, Kawahito Yutaka, Sano Hajime, Nakatani Tatsuya
Department of Urology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abenoku, Osaka 545-8585, Japan.
J Urol. 2003 Nov;170(5):1994-9. doi: 10.1097/01.ju.0000080296.54262.c8.
The metabolism of arachidonic acid by the cyclooxygenase or lipoxygenase pathway generates eicosanoids, which have been implicated in the pathogenesis of various human diseases, including cancer. They are now believed to have important roles in tumor promotion, progression and metastasis. The involvement of lipoxygenase expression and function in tumor growth and metastasis has been reported in human tumor cell lines.
The expression of 5 and 12-lipoxygenase in patients with bladder tumor and chronic cystitis, and in normal bladder tissues was examined. We also examined the effects of their inhibitors on cell proliferation in a bladder cancer cell line. The expression of 5 and 12-lipoxygenase protein was detected by immunohistochemistry. The effects of lipoxygenase inhibitors on bladder cancer cell growth were examined by MTT (3-[4,5-dimethylthiazol-2-thiazolyl]-2,5-diphenyltetrazolium bromide) assay, while Hoechst (Sigma Chemical Co., St. Louis, Missouri) staining was used to determine whether lipoxygenase inhibitors induce apoptosis.
While slight 5 and 12-lipoxygenase expression was detected in chronic cystitis and normal bladder tissues, marked 5 and 12-lipoxygenase expression was detected in bladder cancer tissues. Lipoxygenase inhibitors caused marked inhibition of bladder cancer cells in a concentration and time dependent manner. Cells treated with lipoxygenase inhibitors showed chromatin condensation, cellular shrinkage, small membrane bound bodies (apoptotic bodies) and cytoplasmic condensation.
Lipoxygenase is induced in bladder cancer. Results suggest that lipoxygenase inhibitors may mediate potent antiproliferative effects against bladder cancer cells. Thus, lipoxygenase may become a new target in the treatment of bladder tumors.
花生四烯酸通过环氧化酶或脂氧合酶途径代谢产生类二十烷酸，其与包括癌症在内的多种人类疾病的发病机制有关。现在认为它们在肿瘤促进、进展和转移中起重要作用。已有报道脂氧合酶的表达和功能参与人类肿瘤细胞系中的肿瘤生长和转移。
检测膀胱肿瘤患者、慢性膀胱炎患者及正常膀胱组织中5-脂氧合酶和12-脂氧合酶的表达。我们还研究了其抑制剂对膀胱癌细胞系细胞增殖的影响。通过免疫组织化学检测5-脂氧合酶和12-脂氧合酶蛋白的表达。通过MTT（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐）法检测脂氧合酶抑制剂对膀胱癌细胞生长的影响，同时使用Hoechst（西格玛化学公司，密苏里州圣路易斯）染色来确定脂氧合酶抑制剂是否诱导细胞凋亡。
在慢性膀胱炎和正常膀胱组织中检测到轻微的5-脂氧合酶和12-脂氧合酶表达，而在膀胱癌组织中检测到明显的5-脂氧合酶和12-脂氧合酶表达。脂氧合酶抑制剂以浓度和时间依赖性方式显著抑制膀胱癌细胞。用脂氧合酶抑制剂处理的细胞显示染色质浓缩、细胞皱缩、小的膜结合体（凋亡小体）和细胞质浓缩。
膀胱癌中诱导了脂氧合酶。结果表明脂氧合酶抑制剂可能介导对膀胱癌细胞的强效抗增殖作用。因此，脂氧合酶可能成为治疗膀胱肿瘤的新靶点。
