Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet
Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet
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DOI：
10.1038/bjc.1997.389
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发表时间：
1997-08-01
影响因子：
8.8
通讯作者：
Cameron, IL
中科院分区：
文献类型：
--
作者：
Hardman, WE;Barnes, CJ;Cameron, IL
脂质过氧化产物可能具有细胞毒性。我们的目标是（1）使用两种促氧化剂（铁和一种促氧化药物）选择性地增加食用鱼油的小鼠的植入人类乳腺肿瘤中的脂质过氧化作用，以及（2）杀死癌细胞而不损害正常宿主组织。选择性细胞毒性的理论基础是正常细胞比癌细胞更能处理氧化应激。将食用AIN-76饮食的雄性无胸腺裸小鼠皮下注射至小鼠皮下。MDA-ME 231人乳腺癌细胞。三周后，所有小鼠具有直径为3-10 mm的可触知肿瘤，并且将饮食改变为含有19%鲱鱼鱼油和1%玉米油的改良AIN-76饮食，具有或不具有补充的0.3%柠檬酸铁。2周后，每种饮食（含或不含补充柠檬酸铁的19%鱼油）的一半小鼠注射（每周三次，持续2周）醚-脂质药物edelfosine（ET-18-OCH 3）。柠檬酸铁和ET-18-OCH均显著增加肿瘤中脂质过氧化产物的浓度（通过硫代巴比妥酸反应物质，TEARS测定）。肝脏中的泪液没有增加，也没有证据表明对宿主小鼠有其他有害的副作用。铁的加入增强了肿瘤细胞的死亡，而ET-18-OCH抑制了肿瘤细胞的有丝分裂。使用铁补充剂与ET-18-OCH相结合，导致最慢的生长速率，最低的有丝分裂指数，最高水平的脂质过氧化产物，并增加了肿瘤的细胞毒性指数，而对宿主没有可检测到的伤害。铁补充剂增加肿瘤抑制超过预期的增加眼泪的浓度在肿瘤值得进一步研究。
Lipid peroxidation products can be cytotoxic. Our objectives were (1) to use two pro-oxidants (iron and a pro-oxidative drug) to selectively increase lipid peroxidation in the implanted human breast tumours of mice consuming fish oil and (2) to kill the cancer cells without harming normal host tissues. The theoretical basis for selective cytotoxicity is that normal cells are better able to handle oxidative stress than cancer cells. Male athymic nude mice, consuming an AIN-76 diet, were injected s.c. with MDA-ME 231 human breast carcinoma cells. Three weeks later, ail mice had palpable tumours, 3-10 mm in diameter, and diets were changed to modified AIN-76 diets containing 19% menhaden fish oil and 1% corn oil with or without supplemental 0.3% ferric citrate. After 2 weeks, half of the mice on each diet (19% fish oil with or without supplemental ferric citrate) were injected (three times per week for 2 weeks) with the ether-lipid drug edelfosine (ET-18-OCH3). The concentration of lipid peroxidation products in tumours (as measured by thiobarbituric acid-reactive substances, TEARS) was significantly increased by both ferric citrate and ET-18-OCH,. The TEARS in livers were not increased, nor was there evidence of other harmful side-effects to the host mice. The addition of iron enhanced tumour cell death whereas ET-18-OCH, suppressed tumour cell mitosis. The use of iron supplementation combined with ET-18-OCH, resulted in the slowest growth rate, lowest mitotic index, highest level of lipid peroxidation products and increased the cytotoxic index in tumours without detectable harm to the host. That iron supplementation increased tumour suppression beyond that expected from the increase in the concentration of TEARS in the tumour merits further investigation.