title: A combination of desmopressin and docetaxel inhibit cell proliferation and invasion mediated by urokinase-type plasminogen activator (uPA) in human prostate cancer cells.
abstract: BACKGROUND
  This study was designed to assess the effectiveness of a combination treatment using both desmopressin and docetaxel in prostate cancer treatment. Desmopressin is a well-known synthetic analogue of the antidiuretic hormone vasopressin. It has recently been demonstrated to inhibit tumor progression and metastasis in in vivo models. Docetaxel is widely used for the treatment of castration resistant prostate cancer (CRPC) patients. However, durable responses have been uncommon to date. In this study, we investigated the anti-tumor effect of desmopressin in combination with docetaxel in vitro and in vivo.
  
  
  METHODS
  Two prostate cancer cells (PC3, LNCaP) were treated with different concentrations of desmopressin alone, docetaxel alone, and a combination of desmopressin and docetaxel. Cell proliferation was determined by MTS assay. The anti-invasive and anti-migration potential of desmopressin and in combination with docetaxel were examined by wound healing assay, migration chamber assay, and matrigel invasion assay.
  
  
  RESULTS
  The combination of desmopressin and docetaxel resulted in a significant inhibition of PC3 and LNCaP cell proliferation (p < 0.01). Additionally, cell migration and invasion were also inhibited by the combination when compared to that of either treatment alone in PC3 cells (p < 0.01). The anti-tumor effect of this combination treatment was associated with down-regulation of both urokinase-type plasminogen activator (uPA) and matrix metalloproteinase (MMP-2 and MMP-9) in PC3 cells.
  
  
  CONCLUSIONS
  We are the first to elucidate the anti-tumor and anti-metastatic potential of desmopressin in combination with docetaxel in a prostate cancer model via the uPA-MMP pathway. Our finding could potentially contribute to the therapeutic profile of desmopressin and enhance the efficacy of docetaxel based treatment for CRPC.
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Klotz
authors.affiliation: Department of Pathology, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Sugar
authors.affiliation: Department of Research Design and Biostatistics, Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Center, Toronto, ON, Canada.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kiss
authors.affiliation: Division of Urology, Sunnybrook Health Sciences Center, Toronto, ON, Canada. Electronic address: vasundara.venkateswaran@sunnybrook.ca.
authors.forename: Vasundara
authors.initials: V
authors.lastname: Venkateswaran
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000494:pharmacology*; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D003894:Deamino Arginine Vasopressin
keywords: Desmopressin; Docetaxel; Matrix metalloproteinase; Prostate cancer; uPA