Atorvastatin regulates the migration and invasion of prostate cancer through the epithelial-mesenchymal transformation and matrix metalloproteinase pathways.

Abstract

PurposeOur purpose was to verify the effects of atorvastatin (ATO) on prostate cancer (PCa) proliferation, apoptosis, invasion, and metastasis and to further explore the drug’s mechanism of action.Materials and MethodsWe used cell counting kit-8 (CCK8) and clone formation experiments to study the effect of ATO on the proliferation of PC3 cells. Flow cytometry and Hoechst 33342 staining were used to detect cell apoptosis. Cell migration and invasion were detected through wound healing experiments and transwell experiments. Western blotting was applied to detect apoptosis-related proteins (BAX, Bcl-2, PARP, and Caspase-3), epithelial-mesenchymal transformation (EMT) proteins, and matrix metalloproteinase (MMP) expression. A mouse xenograft tumor model was established, and tumor volume and weight were determined. The expression levels of the above-mentioned proteins were determined through western blot.ResultsATO inhibited PC-3 cell proliferation and promoted cell apoptosis in a dose-dependent manner. ATO significantly up-regulated the expression of BAX, PARP, and Caspase-3 and inhibited the expression of Bcl-2. Wound healing and transwell experiments showed that ATO inhibited invasion and metastasis in PC-3 cells, possibly because ATO could inhibit the EMT and the expression of MMPs in PC-3 cells. Studies in nude mice showed that ATO significantly reduced tumor volume and weight; the expression levels of related proteins were consistent with the in vitro results.ConclusionsATO inhibits the occurrence and development of PCa and regulates the migration and invasion of PCa cells by inhibiting the EMT and MMPs.