Lovastatin Inhibits Tumor Growth and Metastasis Development of a Rat Fibrosarcoma

Abstract

HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate limiting enzime in cholesterol synthesis, catalyses mevalonate production and, hence, influence the synthesis of isoprenoid metabolites. It has already been demonstrated that products of the mevalonate pathway play an important role in the progress of the cell cycle and cell survival. Lovastatin (LOV) competitively 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. Considering that p21ras protein was reported to have a significant rol in metastatic behavior of tumor cells, we decided to study LOV as an antimetastatic agent on a ratfibrosarcoma. We demonstrated that a short treatment with LOV diminished primary tumor growth and the number and size of lung experimental metastasis.