Atorvastatin and Caffeine in Combination Regulates Apoptosis, Migration, Invasion and Tumorspheres of Prostate Cancer Cells.

Atorvastatin is the most prescribed cholesterol-lowering statin, while caffeine enhances chemo-sensitivity and induces apoptosis of tumor cells through its DNA repair-inhibiting effect. The present study investigated the effects and mechanisms of atorvastatin and caffeine in combination on human prostate cancer cells cultured in vitro. Cell growth were determined by the trypan blue exclusion assay. The cell apoptosis and colony formation were determined by morphological assessment. The ability of cell migration and invasion were performed using a scratch wound-healing and Transwell assay. Tumorspheres were formed in suspension under the condition of non-adherence and serum-free medium. Finally, the western blot assay was used to determine the levels of proteins. The combination synergistically suppressed proliferation and induced apoptotic death. Meanwhile, the migration, invasion, and the formation of tumorspheres were significantly inhibited by the combination. We found that atorvastatin and caffeine in combination downregulated phospho-Akt, phospho-Erk1/2, anti-apoptotic Bcl-2 and Survivin protein levels. Results of the present study indicate treatment with the combination of caffeine and atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer and should be evaluated clinically.