Effect of the lipid-lowering agent bezafibrate on tumour growth rate in vivo

Abstract

Summary 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 '4C-lipid from 1-'4C-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.

The role of triglyceride lipases in cancer associated cachexia

“…In addition, lipid-lowering drugs such as benzafibrate induce tumor growth, probably by inducing β-oxidation of FAs in MAC16, a cachexia-inducing adenocarcinoma that is also characterized by increased FA levels in serum [98]. Benzafibrate does not affect tumor growth of non-cachexia-inducing MAC13 adenocarcinoma, presumably because FA serum levels are not increased in this model [98]. Eicosapentaenoic acid inhibits tumor-induced lipolysis and also decreases the growth of MAC16 tumors [99].…”

“…Murine models of cancer have demonstrated that dietary supplements significantly affect tumor growth [94], and the importance of circulating FA in tumor growth has been already reported in murine models of acute fasting or streptozotocin-induced diabetes where increased circulating FA concentration lead to increased tumor proliferation [95–97]. In addition, lipid-lowering drugs such as benzafibrate induce tumor growth, probably by inducing β-oxidation of FAs in MAC16, a cachexia-inducing adenocarcinoma that is also characterized by increased FA levels in serum [98]. Benzafibrate does not affect tumor growth of non-cachexia-inducing MAC13 adenocarcinoma, presumably because FA serum levels are not increased in this model [98].…”

Lipoprotein lipase in non-small cell lung cancer tissue is highly expressed in a subpopulation of tumor-associated macrophages

“…The latter has been proposed to be a reasonable explanation for the fact that high LPL activity in NSCLC tissue (when compared to activity in adjacent non-cancer lung tissue) predicts shorter patient survival, independently of standard prognostic factors [23]. This influx provides lipids as an effective source of energy and for synthesis of the lipid components necessary to sustain tumor growth [13,19]. Other consequences of the increased lipid influx to the tumor have also been proposed, such as unfavorable eicosanoid synthesis, changed membrane phospholipid composition affecting permeability and receptor activity, adverse hormone metabolism and increased free radical formation from fatty acid oxidation [9], which may all favor tumor progression.…”

Diagnostic model based on Raman spectra of normal, hyperplasia and prostate adenocarcinoma tissuesin vitro

“…Also, the presence of cholesterol crystals in CaP tissue is common and could be a characteristic of high-grade lesions. For proteins, studies in oral tissue observed a progressive loss of continuity in the expression of collagen IV and laminin as tissues progressed from dysplasias to metastatic nodules [24]. This relation is important, as more aggressive carcinomas have an increased ability to produce enzymes that degrade basal membrane components, consequently hindering new protein synthesis [24].…”

“…For proteins, studies in oral tissue observed a progressive loss of continuity in the expression of collagen IV and laminin as tissues progressed from dysplasias to metastatic nodules [24]. This relation is important, as more aggressive carcinomas have an increased ability to produce enzymes that degrade basal membrane components, consequently hindering new protein synthesis [24]. Also, the presence of lower protein in CaP tissue, presented in 1663 cm −1 peak, may be explained by decrease of the glutathione S transferase.…”