Effects of cholesterol inhibitor lovastatin on Rho GTPases activity and cytoskeleton formation in MCF-7 breast cancer cells

Objective To investigate the effects of lovastatin (LOV) on Rho GTPases activity and cytoskeleton organization in MCF 7 cells. Methods Expression levels of RhoA, Rac2, and RhoGDI mRNA were determined by RT PCR analysis. GTP binding activity of Rho GTPases was detected by autoradiography. Microfilament and intermediate filament reformations were observed by confocal laser microscopy and electron microscopy. Results After treatment of MCF 7 cells with 4-16 μmol/L LOV for 48-72 h, the expression levels of Rac2 mRNA and RhoGDI mRNA were up regulated, but the binding abilities of Rho GTPases and GTP decreased AT 72 h after treatment. There was no obvious change in the expression of RhoA mRNA. In addition, LOV obviously accelerated the reformation of microfilament and intermediate filament in dose and time dependent manners in MCF 7 cells. Conclusion LOV can inhibit the activation of Rho GTPases through blocking the post translational geranylgeranylpyrophosphate of Rho GTPases, but can obviously promote the cytoskeleton reorganization in MCF 7 cells.