title: Combined effects of atorvastatin and aspirin on growth and apoptosis in human prostate cancer cells.
abstract: Epidemiologic studies indicate the use of either statins or aspirin have beneficial effects in prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of atorvastatin and aspirin alone or in combination in human prostate cancer cells cultured in vitro and grown as xenograft tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in prostate cancer cells were determined by the trypan blue exclusion and propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in Matrigel. After 4-6 weeks, mice with PC-3 tumors received i.p. injections of vehicle, atorvastatin (5 mg/kg), aspirin (80 mg/kg), or atorvastatin (5 mg/kg) + aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of atorvastatin and aspirin had more potent effects on growth inhibition and apoptosis stimulation in prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of atorvastatin and aspirin on inhibiting the growth of prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of atorvastatin and aspirin in patients with prostate cancer.
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Chelsea
authors.initials: C
authors.lastname: Farischon
authors.affiliation: Department of Chemical and Environmental Engineering, Wuyi University, Jiangmen, Guangdong 529020, P.R. China.
authors.forename: Dongli
authors.initials: D
authors.lastname: Li
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Du
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Allan H. Conney Laboratory for Anticancer Research, Guangdong University of Technology, Guangzhou, Guangdong 510006, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Goodin
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000924:Anticholesteremic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000924:Anticholesteremic Agents; D016328:NF-kappa B; D000069059:Atorvastatin; D048049:Extracellular Signal-Regulated MAP Kinases; D001241:Aspirin