title: Mechanistic Study of Inhibitory Effects of Atorvastatin and Docetaxel in Combination on Prostate Cancer.
abstract: OBJECTIVE
  To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells.
  
  
  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.
authors.affiliation: 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.
authors.forename: Xuan
authors.initials: X
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.affiliation: Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Guangdong Food and Drug Vocational College, Guangzhou, P.R. China.
authors.forename: Daiying
authors.initials: D
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Kaylyn
authors.initials: K
authors.lastname: Hung
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A.
authors.forename: Susan
authors.initials: S
authors.lastname: Goodin
authors.affiliation: 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. xizheng@pharmacy.rutgers.edu.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D000069059:Atorvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000494:pharmacology; D000077143:Docetaxel; D004357:Drug Synergism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D014158:Transcription, Genetic
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D043823:Taxoids; D000077143:Docetaxel; D002784:Cholesterol; D000069059:Atorvastatin
keywords: Combination treatment; atorvastatin; docetaxel; prostate cancer