Modulation of metastatic ability by inhibition of cholesterol synthesis

Synvinolin (MK-733), a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) depressing de novo synthesis of cholesterol, was given to BN472 tumor cells in culture medium, 2 days prior to i.v. injection of the cells into syngeneic rats. Another group of rats received cells cultured under the same conditions but without synvinolin. Two different types of culture medium were used, a 'complete' medium (Hybridoma) and a medium (RPMI 1640) to which 1 per cent of fetal calf serum (FCS) was added. Tumor cells cultured in the presence of synvinolin showed significantly lower cholesterol values than untreated cells. Tumor cells treated with synvinolin had a decreased ability to form metastatic nodules when compared with control cells. The results supply further evidence for the suggestion that cholesterol modulates the ability of mononuclear cells to eliminate tumor cells, although it cannot be excluded that alteration of cell growth plays an important role as well.