Simvastatin effects on a human lung carcinoma and cholesterol homeostasis of host and non-host mice.
In order to investigate the effect of a competitive inhibitor of the HMG-CoA reductase on tumor growth and cholesterol homeostasis of host and non-host mice, we maintained a human lung mucoepidermoid carcinoma (HLMC) in nude mice, treating these animals with Simvastatin for 33 days. The drug increased the total activity of hepatic HMG-CoA reductase without affecting the cholesterolemia. Non-treated host animals presented lower serum, tissue and microsomal hepatic cholesterol than non-host animals. These differences disappeared when animals were treated with Simvastatin, though the induction of the reductase activity at mid-dark was higher in non-host than in host animals. Simvastatin produced no significant effects on both final tumor volume and body weight. Synthesis and cholesterol homeostasis restoration induced by liver and tumoral reductase would account for no effect on the HLMC growth after a long treatment with Simvastatin.
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Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP) y Area Ciencias Biológicas del Departamento de Introducción a la Medicina, Facultad de Cs. Médicas, UNLP-CONICET, La Plata, Argentina.
de Bravo
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D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D018277:Carcinoma, Mucoepidermoid / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008862:Microsomes, Liver / Q000201:enzymology; D009368:Neoplasm Transplantation; D019821:Simvastatin / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D002784:Cholesterol; D019821:Simvastatin; D006903:Hydroxymethylglutaryl CoA Reductases