The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells.
BACKGROUND
A number of recent studies have suggested that cancer incidence rates may be lower in patients receiving statin treatment for hypercholesterolemia. We examined the effects of statin drugs on in vitro proliferation, migration and invasion of melanoma cells.


METHODS
The ability of lovastatin, mevastatin and simvastatin to inhibit the melanoma cell proliferation was examined using cytotoxicity and apoptosis assays. Effects on cell migration and invasion were assessed using transwell invasion and migration chambers. Hypothesis testing was performed using 1-way ANOVA, and Student's t-test.


RESULTS
Lovastatin, mevastatin and simvastatin inhibited the growth, cell migration and invasion of HT144, M14 and SK-MEL-28 melanoma cells. The concentrations required to inhibit proliferation of melanoma cells (0.8-2.1 microave previously been achieved in a phase I clinical trial of lovastatin in patients with solid tumours, (45 mg/kg/day resulted in peak plasma concentrations of approximately 3.9 micro


CONCLUSIONS
Our results suggest that statin treatment is unlikely to prevent melanoma development at standard doses. However, higher doses of statins may have a role to play in adjuvant therapy by inhibiting growth and invasion of melanoma cells.
Glynn
Sharon A
SA
National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland. glynnsh@mail.nih.gov
O'Sullivan
Dermot
D
Eustace
Alex J
AJ
Clynes
Martin
M
O'Donovan
Norma
N
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D009361:Neoplasm Invasiveness; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C012258:mevastatin; D008148:Lovastatin; D019821:Simvastatin