METASTASIS OF B16F10 MOUSE MELANOMA INHIBITED BY LOVASTATIN, AN INHIBITOR OF CHOLESTEROL-BIOSYNTHESIS

Lovastatin (LST) is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzym e A (HMG-CoA) reductase, a rate-limiting enzyme that regulates the bio synthesis of cholesterol. This drug is used clinically to treat patien ts with hypercholesterolemia. Numerous studies have also suggested an important, if not essential, role of the cholesterol biosynthetic path way to cell growth and proliferation. In fact, recent studies demonstr ating the inhibitory effects of LST on various tumor cells have drawn much attention. We now describe a novel action of LST that inhibited e xperimental lung metastasis of the highly metastatic B16F10 mouse mela noma in nude mice. Further, when used in in vitro studies, LST pretrea tment of B16F10 cells resulted in inhibition of attachment, motility, and invasion, which are key steps in the dynamic sequence of events th at comprise the metastatic cascade. Our studies also suggested that th e antimetastatic effect of LST on B16F10 cells is probably not mediate d by a growth inhibitory action. We submit that these observations ide ntify an antimetastatic agent with potentially useful clinical applica tion.