Hardman W E, Moyer M P, Cameron I L
Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 78284, USA.
Br J Cancer. 1999 Oct;81(3):440-8. doi: 10.1038/sj.bjc.6690713.
The cancer chemotherapeutic efficacy of the topoisomerase I inhibitor, CPT-11 (irinotecan) is often limited by the induction of severe delayed diarrhoea. In animal studies, CPT-11 use is associated with histopathological damage to the mucosa of the small and large intestines. Results from the present study demonstrate that 60 mg CPT-11 per kg body weight (i.v. q4d x 6) halted the growth, but did not cause significant regression, of MCF7 human breast carcinoma xenografts in mice fed a diet containing 7% corn oil. However, when the diet of the MCF7-bearing mice was supplemented with 3% or 6% fish oil, the same CPT-11 treatment caused significant regression of the MCF7 xenograft. Histomorphometric analyses of intestinal mucosa of mice treated with CPT-11 and fed the diet containing 7% com oil indicated that treatment with CPT-11 induced structural changes in the intestinal mucosa which persisted at least 5 days after the last dose of CPT-11. The intestinal mucosal architecture of mice that were treated with CPT-11 and fed the diets containing fish oil was largely unchanged from the architecture of the group of mice which did not receive CPT-11. These findings indicate that fish oil supplements may be a useful adjunct to CPT-11 treatment.
拓扑异构酶I抑制剂CPT-11(伊立替康)的癌症化疗疗效常常受到严重迟发性腹泻的限制。在动物研究中,使用CPT-11会导致小肠和大肠黏膜的组织病理学损伤。本研究结果表明,在喂食含7%玉米油饮食的小鼠中,每千克体重60毫克CPT-11(静脉注射,每4天一次,共6次)可抑制MCF7人乳腺癌异种移植瘤的生长,但未引起显著消退。然而,当给携带MCF7的小鼠饮食中添加3%或6%的鱼油时,相同的CPT-11治疗导致MCF7异种移植瘤显著消退。对接受CPT-11治疗并喂食含7%玉米油饮食的小鼠肠黏膜进行组织形态计量分析表明,CPT-11治疗可诱导肠黏膜结构改变,这种改变在最后一剂CPT-11后至少持续5天。接受CPT-11治疗并喂食含鱼油饮食的小鼠的肠黏膜结构与未接受CPT-11治疗的小鼠组的结构基本没有变化。这些发现表明,补充鱼油可能是CPT-11治疗的一种有用辅助手段。