Mechanistic Study of Inhibitory Effects of Atorvastatin and Docetaxel in Combination on Prostate Cancer.

AIM - To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells.

MATERIALS AND METHODS - Cell growth and apoptosis were determined by the trypan blue exclusion assay and morphological assessment of cells was performed with propidium iodide.

NF-κB activity was determined by luciferase reporter gene assay and the western blot assay was used to determine the levels of Bcl-2, phospho-Akt, VEGF, and phospho-Erk1/2.

RESULTS - Results showed that following pre-treatment with cholesterol, resistance of PC-3 prostate cancer cells to docetaxel was increased. The combination of docetaxel with atorvastatin potently inhibited growth and induced apoptosis in PC-3 cells. Mechanistic studies indicated that induction of apoptosis in PC-3 cells was associated with significant decreases in the levels of Bcl-2, VEGF, phosphor-Akt, and phosphor-Erk1/2.

CONCLUSIONS - Treatment with cholesterol decreased the sensitivity of prostate cancer cells to docetaxel. Docetaxel in combination with cholesterol-lowering drugs such as atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer.

Cancer genomics & proteomics. 0000 [Epub]

Xuan Chen, Yue Liu, Jian Wu, Huarong Huang, Zhiyun DU, Kun Zhang, Daiying Zhou, Kaylyn Hung, Susan Goodin, X I Zheng

Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A., Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A., The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China., Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China., Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China., Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China., Guangdong Food and Drug Vocational College, Guangzhou, P.R. China., Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A., Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A., Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. 

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