Lovastatin inhibits tumor growth and metastasis development of a rat fibrosarcoma.
HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, the rate limiting enzyme 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 non-sterol isoprenoids, such as farnesyl residues. The posttranslational 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 rat fibrosarcoma. We demonstrated that a short treatment with LOV diminished primary tumor growth and the number and size of lung experimental metastasis.
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Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Argentina.
Rozados
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Roggero
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EA
Scharovsky
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OG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D005354:Fibrosarcoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008148:Lovastatin / Q000627:therapeutic use*; D008297:Male; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D011919:Rats, Inbred Strains; D012513:Sarcoma, Experimental / Q000097:blood / Q000188:drug therapy / Q000473:pathology
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin