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. 1991 Dec;64(6):1035–1038. doi: 10.1038/bjc.1991.460

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

H D Mulligan 1, M J Tisdale 1
PMCID: PMC1977866  PMID: 1764364

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abraham S., Hillyard L. A. Effect of dietary 18-carbon fatty acids on growth of transplantable mammary adenocarcinomas in mice. J Natl Cancer Inst. 1983 Sep;71(3):601–605. [PubMed] [Google Scholar]
  2. Beck S. A., Tisdale M. J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 1987 Nov 15;47(22):5919–5923. [PubMed] [Google Scholar]
  3. Bibby M. C., Double J. A., Ali S. A., Fearon K. C., Brennan R. A., Tisdale M. J. Characterization of a transplantable adenocarcinoma of the mouse colon producing cachexia in recipient animals. J Natl Cancer Inst. 1987 Mar;78(3):539–546. [PubMed] [Google Scholar]
  4. Briddon S., Beck S. A., Tisdale M. J. Changes in activity of lipoprotein lipase, plasma free fatty acids and triglycerides with weight loss in a cachexia model. Cancer Lett. 1991 Apr;57(1):49–53. doi: 10.1016/0304-3835(91)90062-m. [DOI] [PubMed] [Google Scholar]
  5. Fallon H. J., Adams L. L., Lamb R. G. A review of studies on the mode of action of clofibrate and betabenzalbutyrate. Lipids. 1972 Feb;7(2):106–109. doi: 10.1007/BF02532596. [DOI] [PubMed] [Google Scholar]
  6. Glasgow W. C., Eling T. E. Epidermal growth factor stimulates linoleic acid metabolism in BALB/c 3T3 fibroblasts. Mol Pharmacol. 1990 Oct;38(4):503–510. [PubMed] [Google Scholar]
  7. Greene H. L., Herman R. H., Zakim D. The effect of clofibrate on rat tissue adenyl cyclase. Proc Soc Exp Biol Med. 1970 Sep;134(4):1035–1038. doi: 10.3181/00379727-134-34938. [DOI] [PubMed] [Google Scholar]
  8. Lombardi P., Norata G., Maggi F. M., Canti G., Franco P., Nicolin A., Catapano A. L. Assimilation of LDL by experimental tumours in mice. Biochim Biophys Acta. 1989 Jun 28;1003(3):301–306. doi: 10.1016/0005-2760(89)90236-1. [DOI] [PubMed] [Google Scholar]
  9. Lyon I., Kannan R., Ookhtens M., Baker N. Turnover and transport of plasma very-low-density lipoprotein triglycerides in mice bearing Ehrlich ascites carcinoma. Cancer Res. 1982 Jan;42(1):132–138. [PubMed] [Google Scholar]
  10. MEDES G., THOMAS A., WEINHOUSE S. Metabolism of neoplastic tissue. IV. A study of lipid synthesis in neoplastic tissue slices in vitro. Cancer Res. 1953 Jan;13(1):27–29. [PubMed] [Google Scholar]
  11. Manne V., Roberts D., Tobin A., O'Rourke E., De Virgilio M., Meyers C., Ahmed N., Kurz B., Resh M., Kung H. F. Identification and preliminary characterization of protein-cysteine farnesyltransferase. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7541–7545. doi: 10.1073/pnas.87.19.7541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mermier P., Baker N. Flux of free fatty acids among host tissues, ascites fluid, and Ehrlich ascites carcinoma cells. J Lipid Res. 1974 Jul;15(4):339–351. [PubMed] [Google Scholar]
  13. Mulligan H. D., Tisdale M. J. Lipogenesis in tumour and host tissues in mice bearing colonic adenocarcinomas. Br J Cancer. 1991 May;63(5):719–722. doi: 10.1038/bjc.1991.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nilsson-Ehle P., Schotz M. C. A stable, radioactive substrate emulsion for assay of lipoprotein lipase. J Lipid Res. 1976 Sep;17(5):536–541. [PubMed] [Google Scholar]
  15. Oller do Nascimento C. M., Williamson D. H. Evidence for conservation of dietary lipid in the rat during lactation and the immediate period after removal of the litter. Decreased oxidation of oral [1-14C]triolein. Biochem J. 1986 Oct 1;239(1):233–236. doi: 10.1042/bj2390233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rose D. P., Connolly J. M. Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Res. 1990 Nov 15;50(22):7139–7144. [PubMed] [Google Scholar]
  17. Sauer L. A., Dauchy R. T. Blood nutrient concentrations and tumor growth in vivo in rats: relationships during the onset of an acute fast. Cancer Res. 1987 Feb 15;47(4):1065–1068. [PubMed] [Google Scholar]
  18. Sauer L. A., Dauchy R. T. Identification of linoleic and arachidonic acids as the factors in hyperlipemic blood that increase [3H]thymidine incorporation in hepatoma 7288CTC perfused in situ. Cancer Res. 1988 Jun 1;48(11):3106–3111. [PubMed] [Google Scholar]
  19. Sauer L. A., Dauchy R. T. Stimulation of tumor growth in adult rats in vivo during acute streptozotocin-induced diabetes. Cancer Res. 1987 Apr 1;47(7):1756–1761. [PubMed] [Google Scholar]
  20. Spector A. A. Fatty acid metabolism in tumors. Prog Biochem Pharmacol. 1975;10:42–75. [PubMed] [Google Scholar]
  21. Spector A. A., Soboroff J. M. Effect of chlorophenoxyisobutyrate on free fatty acid utilization by mammalian cells. Proc Soc Exp Biol Med. 1971 Jul;137(3):945–947. doi: 10.3181/00379727-137-35701. [DOI] [PubMed] [Google Scholar]
  22. Stansbie D., Brownsey R. W., Crettaz M., Denton R. M. Acute effects in vivo of anti-insulin serum on rates of fatty acid synthesis and activities of acetyl-coenzyme A carboxylase and pyruvate dehydrogenase in liver and epididymal adipose tissue of fed rats. Biochem J. 1976 Nov 15;160(2):413–416. doi: 10.1042/bj1600413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tisdale M. J., Beck S. A. Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid. Biochem Pharmacol. 1991 Jan 1;41(1):103–107. doi: 10.1016/0006-2952(91)90016-x. [DOI] [PubMed] [Google Scholar]
  24. Tisdale M. J., Brennan R. A., Fearon K. C. Reduction of weight loss and tumour size in a cachexia model by a high fat diet. Br J Cancer. 1987 Jul;56(1):39–43. doi: 10.1038/bjc.1987.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tsai M. H., Yu C. L., Wei F. S., Stacey D. W. The effect of GTPase activating protein upon ras is inhibited by mitogenically responsive lipids. Science. 1989 Jan 27;243(4890):522–526. doi: 10.1126/science.2536192. [DOI] [PubMed] [Google Scholar]

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