title: Lenalidomide enhances the anti-prostate cancer activity of docetaxel in vitro and in vivo.
abstract: BACKGROUND
  In this study, we investigated the effects of combining lenalidomide and docetaxel on in vitro and in vivo models of prostate cancer as a potential strategy for treatment of castrate resistant prostate cancer (CRPC).
  
  
  METHODS
  The effects of combining lenalidomide and docetaxel on proliferation, apoptosis, invasive potential, anchorage independent growth, and p53 activation in the PC3 and DU145 prostate cell lines were investigated. The effects of the lenalidomide and docetaxel combination on LNCaP prostate cancer cell growth and invasiveness in vitro was also studied. The combination of these two agents was finally tested on a xenograft model of PC3 tumor growth in nude mice.
  
  
  RESULTS
  Lenalidomide decreased the IC(50) of docetaxel by up to 50% (P < 0.05) and also decreased invasion in PC3, LNCaP, and DU145 cells and anchorage independent growth in PC3 cells (P < 0.01). Apoptosis in lenalidomide/docetaxel-treated cells was increased by 2.2-fold over single agent docetaxel and a corresponding increase in p53, p38, and BAD activation was observed in Western blots (P < 0.001). When PC3 challenged mice were treated with lenalidomide and docetaxel, median survival increased from 48 to 59 days and the rate of tumor growth was significantly reduced (P < 0.05).
  
  
  CONCLUSIONS
  Lenalidomide may be a promising candidate for combination with docetaxel in the treatment of CRPC.
authors.affiliation: Centre for Infection and Immunity, Division of Clinical Sciences, St George's University of London, London SW17 0RE, UK.
authors.forename: J Y
authors.initials: JY
authors.lastname: Henry
authors.forename: L
authors.initials: L
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Adams
authors.forename: B
authors.initials: B
authors.lastname: Meyer
authors.forename: J B
authors.initials: JB
authors.lastname: Bartlett
authors.forename: A G
authors.initials: AG
authors.lastname: Dalgleish
authors.forename: C
authors.initials: C
authors.lastname: Galustian
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D000077143:Docetaxel; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D066298:In Vitro Techniques; D000077269:Lenalidomide; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use*; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D013792:Thalidomide; D000077269:Lenalidomide