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Int J Oncol. 2003 Oct;23(4):1173-8.

Inhibition of lysophosphatidic acid-induced RhoA activation and tumor cell invasion by 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors.

Author information

1
Department of Tumor Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan. kusama-to@mail.mc.pref.osaka.jp

Abstract

The mevalonate metabolic pathway is necessary for the isoprenylation of a number of small GTPases. We have previously presented that Rho plays a pivotal role in 1-oleoyl-lysophosphatidic acid (LPA)-induced invasion of rat ascites hepatoma MM1 cells. Herein we report the effect of HMG-CoA reductase inhibitors, fluvastatin and lovastatin, on the in vitro invasion of MM1 cells. Fluvastatin and lovastatin inhibited LPA-induced MM1 cell invasion in a dose-dependent manner. Fluvastatin inhibited LPA-induced translocation of RhoA protein from the cytosol to the membrane and RhoA activation which was measured by pull-down assay for GTP-bound RhoA. Fluvastatin also inhibited the translocation of both endogenous and dominant-active RhoA from the cytosol to the membrane, actin stress fiber assembly and in vitro invasion of the cells expressing dominant-active RhoA (Val14-RhoA). These results indicate that HMG-CoA reductase inhibitors have the potential to reduce RhoA activation and cancer cell invasion by targeting the Rho protein isoprenylation.

PMID:
12964001
[Indexed for MEDLINE]

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