ABSTRACT
This review explores the evidence supporting a potential benefit of statins in cancer. In particular, the lipophilic forms (i.e. lovastatin, simvastatin, or similar) would have a therapeutic but not a preventive role. The pleiotropic effects that statins possess mainly explain this phenomenon, influencing the natural history of disease and the response to currently available therapies. By inhibiting the mevalonate pathway, statins would have a systemic effect, similar to that observed in atherosclerosis, reducing the inflammatory stimuli present in the tumor micro-environment and inhibiting the activation of intracellular signaling cascades critical for proliferation, migration/invasion and metastasis of the cancer cell. Despite all this evidence, randomized trials are needed to confirm the benefit of statins on cancer, before promoting their widespread use as a therapeutic or preventive strategy for this condition.
Subject(s)
Animals , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Neoplasms/prevention & control , Antineoplastic Agents/therapeutic use , Atherosclerosis/drug therapy , Atherosclerosis/etiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/complications , Neoplasms/chemically inducedABSTRACT
AIM: To investigate the effect of fluvastatin on the proliferation of vascular smooth muscle cells derived from spontaneously hypertensive rats. METHODS: The aorta smooth muscle cells(ASMCs) of spontaneously hypertensive rats were cultured, and proliferation of cells were detected by measuring cell number and -thymidine(-TdR) incorporation after incubation with Ang Ⅱ, PDGF, fluvastatin and mevalonate acid. RESULTS: (1) The increased cell number and -TdR incorporation stimulated with AngII(10 -6 mol/L) and PDGF(10 ?g/L) were significantly inhibited by fluvastatin in a concentration-dependent manner (10 -5 -10 -7 mol/L); (2) The inhibitory effect of fluvastatin was almost completely reversed by mevalonate acid(10 -3 mol/L). CONCLUSION: The proliferation of ASMCs induced by Ang Ⅱ and PDGF was inhibited by fluvastatin, suggesting that mevalonate acid pathway may play an important role in the proliferation of ASMCs.