HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate limitin
g enzime in cholesterol synthesis, catalyses mevalonate production and, hen
ce, influence the synthesis of isoprenoid metabolites. It hers already been
demonstrated that products of the mevalonate pathway play an important rol
e in the progress of the cell cycle and cell survival. Lovastatin (LOV) com
petitively inhibits HMG-CoA reductase, blocking the synthesis of mevalonic
acid and the generation of nonsterol isoprenoids, such as farnesyl residues
. The posttranlational farnesylation of p21ras protein is essential for its
binding to the membrane and, therefore, for its transforming activity. Con
sidering that p21ras protein was reported to have a significant rol in meta
static behavior of tumor cells, we decided to study LOV as an antimetastati
c agent on a rat fibrosarcoma. We demonstrated that a short treatment with
LOV diminished primary tumor growth and the number and size of lung experim
ental metastasis.