Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo.
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.
Mulligan
H D
HD
Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Tisdale
M J
MJ
D000818:Animals; D001629:Bezafibrate / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D014304:Triolein / Q000378:metabolism; D014407:Tumor Cells, Cultured
D014304:Triolein; D001629:Bezafibrate