Mulligan H D, Tisdale M J
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Br J Cancer. 1991 Dec;64(6):1035-8. doi: 10.1038/bjc.1991.460.
The growth rate of the MAC16 tumour in cachectic animals was significantly enhanced by the hypolipidemic agent bezafibrate, while the growth rate of a histologically similar tumour, the MAC13, which grows without an effect on host body compartments was unaffected. Growth of the MAC16 in vitro was unaffected by bezafibrate, suggesting that it was an in vivo phenomenon only. The stimulatory effect of bezafibrate correlated with the maximum plasma levels of free fatty acids (FFA) arising from the catabolism of adipose tissue. Accumulation of 14C-lipid from 1-14C-triolein administered by intragastric intubation was enhanced in heart, gastrocnemius muscle and tumour of bezafibrate treated animals, while the total lipid absorption did not differ from solvent treated controls. The increased lipid accumulation in the heart, but not the tumour correlated with an increased tissue lipoprotein lipase level. The increased tumour level may arise from an increased uptake of FFA arising from a weakening of the bonds between FFA and albumin. These results suggest that growth of certain tumours is dependent on maintaining sufficient lipid levels and that the lipid mobilising effect of the tumour may be necessary to sustain tumour growth.
在恶病质动物中,降血脂药物苯扎贝特显著提高了MAC16肿瘤的生长速率,而组织学上类似的MAC13肿瘤(其生长对宿主体腔无影响)的生长速率则不受影响。苯扎贝特对MAC16肿瘤的体外生长没有影响,这表明这仅是一种体内现象。苯扎贝特的刺激作用与脂肪组织分解代谢产生的游离脂肪酸(FFA)的最高血浆水平相关。通过胃内插管给予的1-14C-三油酸甘油酯中14C-脂质在苯扎贝特处理动物的心脏、腓肠肌和肿瘤中的蓄积增强,而总脂质吸收与溶剂处理的对照组无差异。心脏中脂质蓄积的增加与组织脂蛋白脂肪酶水平的升高相关,但肿瘤中脂质蓄积的增加并非如此。肿瘤中脂质水平的升高可能源于FFA与白蛋白之间结合力减弱导致FFA摄取增加。这些结果表明,某些肿瘤的生长依赖于维持足够的脂质水平,并且肿瘤的脂质动员效应可能是维持肿瘤生长所必需的。