Treatment > Carmustine · Chemotherapy-Enhancing Agents

Abstract

Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells

Soma MR, Pagliarini P, Butti G, Paoletti R, Paoletti P, Fumagalli R

Institute of Pharmacological Sciences, University of Milan, Italy

The effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on human glioma cell growth was investigated.
When incubated with simvastatin, cell proliferation decreased in a concentration-dependent fashion, as measured by cell number and [3H]-thymidine incorporation into DNA (concentration producing 50% inhibition, 60 nM).
The effect was detectable 12 h after cells were exposed to the drug and persisted for 2 days.
Addition of mevalonate to cells exposed effect of simvastatin in combination with beta-interferon and N,N'-bis(2-chloroethyl)-N-nitrosourea, both antitumoral drugs, was also evaluated by cell growth inhibition assay.
The concentration producing 50% inhibition for each of these drugs was 650 units/ml and 50 nM, respectively.
Subliminal concentrations of beta-interferon or N,N'-bis(2-chloroethyl)-N-nitrosourea were incubated together with 1 nM simvastatin.
The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity.
Simultaneous cell exposure to simvastatin with either N,N'-bis(2-chloroethyl)-N-nitrosourea or beta-interferon produced a strong synergistic inhibitory effect on cell proliferation.
These data provide in vitro support for the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, utilized as plasma cholesterol-lowering agents, could potentiate the effect of antiblastic drugs on tumor growth.

PMID: 1643632 [PubMed - indexed for MEDLINE]