Lovastatin inhibits tumor growth and metastasis development of a rat fibrosarcoma

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.