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Simvastatin effects on a human lung carcinoma and cholesterol homeostasis of host and non-host mice
1Instituto 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.
Abstract:
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.
Insights
Simvastatin, a HMG-CoA reductase inhibitor, did not affect tumor growth in mice. Cholesterol homeostasis was restored by Simvastatin, explaining its lack of impact on human lung mucoepidermoid carcinoma (HLMC) growth.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- HMG-CoA reductase is a key enzyme in cholesterol synthesis.
- Statins are competitive inhibitors of HMG-CoA reductase.
- Tumor growth can be influenced by host cholesterol homeostasis.
Purpose of the Study:
- To investigate the effect of Simvastatin on tumor growth and cholesterol homeostasis.
- To determine if Simvastatin impacts human lung mucoepidermoid carcinoma (HLMC) in mice.
Main Methods:
- Human lung mucoepidermoid carcinoma (HLMC) cells were implanted in nude mice.
- Mice were treated with Simvastatin for 33 days.
- Hepatic HMG-CoA reductase activity, cholesterolemia, and cholesterol levels were measured.
Main Results:
- Simvastatin increased hepatic HMG-CoA reductase activity but did not affect cholesterolemia.
- Simvastatin treatment normalized cholesterol levels between host and non-host animals.
- Simvastatin had no significant effect on tumor volume or body weight.
Conclusions:
- Simvastatin restored cholesterol homeostasis in host and non-host mice.
- Restoration of cholesterol homeostasis and compensatory synthesis likely explains the lack of Simvastatin's effect on HLMC growth.
- HMG-CoA reductase inhibition alone may not be sufficient to inhibit HLMC tumor progression.