Inhibitory effect of Lovastatin on spontaneous metastases derived from a rat lymphoma.
The HMGCoA reductase inhibitor Lovastatin (LOV) has previously shown to abrogate p21ras farnesylation, which is associated with invasive and metastatic abilities in many tumor models. Considering the scarcity of therapeutic resources against metastasis, our objective was to study LOV as an antimetastatic agent on L-TACB rat lymphoma, which as a syngeneic tumor model resembles more closely the situation in human cancer. We also aimed to analyze the effect of LOV on chemoinvasion, motility, metalloproteases secretion, angiogenic capacity, and adhesion to the reconstituted basement membrane Matrigel. Our results showed that LOV caused no effect on cell motility, metalloprotease secretion and neovascularization. Conversely, LOV produced a significant inhibition of invasiveness, which could be a consequence of an impaired cell adhesion to the basement membrane observed. These effects could explain, at least in part, the inhibitory action of LOV on L-TACB rat lymphoma metastases.
Matar
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Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Argentina.
Rozados
V R
VR
Binda
M M
MM
Roggero
E A
EA
Bonfil
R D
RD
Scharovsky
O G
OG
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004354:Drug Screening Assays, Antitumor; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008148:Lovastatin / Q000627:therapeutic use*; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009361:Neoplasm Invasiveness; D009389:Neovascularization, Pathologic; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D008148:Lovastatin