Simvastatin as an immunomodulator and anti-myeloma agent - epidemiological, in vitro and murine model studies.

INTRODUCTION

Simvastatin (SIM), a member of the statin family, is commonly used to lower blood cholesterol levels, particularly low-density lipoprotein. Statins inhibit the action of hydroxy-methyl-glutaryl-coenzyme A reductase, an important enzyme in the synthesis of cholesterol and isoprenoids; they also have anti-inflammatory effects and can regulate membrane synthesis in cancer cells. Preliminary evidence suggests an association between SIM use and reduced cancer incidence. SIM's anti-cancer efficacy in vivo has been shown in studies on several solid tumors, but little is known about its effects on hematological cancers, such as Multiple Myeloma (MM).

METHODS

Initially, we searched for such as an association in a large community database and observed a significantly lower MM incidence among SIM users. We proceeded to test the effect of SIM on both murine and human MM cell lines and the tested the effect of long-term SIM treatment on development of MM in an animal model.

RESULTS

SIM exposure led to apoptosis in both murine and human MM cell lines. We show that long-term intake of SIM reduced tumor load and positively impacted bone marrow CD8+ T levels as well as cell-mediated anti-myeloma cytotoxicity. SIM treatment also elevated the total IgA and IgG serum concentrations in healthy mice.

CONCLUSIONS

These results suggest that SIM, which many adults use to control cholesterol levels, may play a dual role in the management of MM, by influencing membrane synthesis in myeloma cells leading to apoptotic cell death and enhancing the T-cell mediated anti-tumor cell response in MM.