Tatsuta M, Iishi H, Baba M, Uehara H, Nakaizumi A
Department of Gastrointestinal Oncology, Center for Adult Diseases-Osaka, Japan.
Carcinogenesis. 1995 Apr;16(4):941-2. doi: 10.1093/carcin/16.4.941.
The effects of amiloride on the incidence and histology of colon tumors induced by azoxymethane, on the labeling index of the colon mucosa and on the activity of ornithine decarboxylase in the colon wall were investigated in Wistar rats. Rats received 10 weekly injections of 7.4 mg/kg body wt azoxymethane and s.c. injections of 5 or 7.5 mg/kg body wt amiloride in depot form every other day for 35 weeks. Prolonged administration of amiloride at a dose of 7.5 mg/kg, but not 5 mg/kg, significantly reduced the incidence of colon tumors at week 35. However, administration of amiloride had little or no significant influence on the histological types of colon tumors and cancers. Administration of amiloride at 7.5 mg/kg significantly decreased the labeling index of the colon mucosa and ornithine decarboxylase activity in the colon wall during and after administration of azoxymethane. These findings suggest that amiloride inhibits development of colon tumors. A possible mechanism of inhibition of colon carcinogenesis by amiloride is its suppression of proliferation of colon tumor cells.
在Wistar大鼠中，研究了氨氯吡咪对由氧化偶氮甲烷诱导的结肠肿瘤的发生率和组织学、对结肠黏膜标记指数以及对结肠壁中鸟氨酸脱羧酶活性的影响。大鼠每周接受10次7.4毫克/千克体重的氧化偶氮甲烷注射，并每隔一天皮下注射5或7.5毫克/千克体重的长效氨氯吡咪，持续35周。以7.5毫克/千克的剂量长期给予氨氯吡咪（而非5毫克/千克），在第35周时显著降低了结肠肿瘤的发生率。然而，氨氯吡咪的给药对结肠肿瘤和癌症的组织学类型几乎没有显著影响。在给予氧化偶氮甲烷期间及之后，以7.5毫克/千克剂量给予氨氯吡咪显著降低了结肠黏膜的标记指数以及结肠壁中的鸟氨酸脱羧酶活性。这些发现表明氨氯吡咪抑制结肠肿瘤的发展。氨氯吡咪抑制结肠癌发生的一种可能机制是其对结肠肿瘤细胞增殖的抑制作用。
