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

Cancer Genomics - Proteomics

DAIYING ZHOU¹  ZHIYUN DU⁴  YUE LIU³  JIAN WU⁵  SUSAN GOODIN⁶  KUN ZHANG⁴  KAYLYN HUNG³  HUARONG HUANG⁴  XI ZHENG²  XUAN CHEN² 

[1] uangdong Food and Drug Vocational College, Guangzhou, P.R. Chinauangdong Food and Drug Vocational College, Guangzhou, P.R. Chinauangdong Food and Drug Vocational College, Guangzhou, P.R. China;aboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinausan 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.aboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinaaboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinausan 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.usan 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.aboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinausan 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.;usan 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.usan 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.usan 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.;aboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinaaboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. Chinaaboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China;he Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. Chinahe Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. Chinahe Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China;utgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A.utgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A.utgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A.

关键词: Combination treatment;    prostate cancer;    docetaxel;    atorvastatin;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

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. Conclusion: 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.

【 授权许可】

Unknown