title: Targeted therapy with fatty acid synthase inhibitors in a human  prostate carcinoma LNCaP/tk-luc-bearing animal model.
abstract: BACKGROUND
  Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects.
  
  
  METHODS
  We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging.
  
  
  RESULTS
  FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mgkg(-1); 30 mgkg(-1) once a week or 15 mgkg(-1) twice a week for 4 weeks) and siFASN (1.4 mgkg(-1) every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control.
  
  
  CONCLUSIONS
  The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.
authors.affiliation: Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: H-W
authors.initials: HW
authors.lastname: Chen
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chang
authors.forename: H-Y
authors.initials: HY
authors.lastname: Chuang
authors.forename: W-T
authors.initials: WT
authors.lastname: Tai
authors.forename: J-J
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D057054:Molecular Imaging; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D064429:Fatty Acid Synthases