Abstract

BACKGROUND/AIM: Epithelial-mesenchymal transition (EMT) via Sonic Hedgehog (Shh) signaling may be one of the mechanisms of progression of castration-resistant prostate cancer (CRPC). In this study, we investigated the possible therapeutic effect of vismodegib, a new Shh inhibitor, in a mouse CRPC model.

MATERIALS AND METHODS: We determined cell proliferation, apoptosis and the expression of EMT-related genes for three prostate cancer cell lines; androgen-dependent LNCaP and independent C4-2B and PC-3 in the presence of vismodegib in vitro. Fifty mg/kg of vismodegib were orally administered into mice bearing C4-2B and PC-3 tumors, respectively every other week for 3 weeks.

RESULTS: Vismodegib significantly inhibited cell proliferation and induced cell apoptosis in all cell lines in vitro (p<0.05). Vismodegib significantly inhibited EMT in CRPC cells and tumor growth in C4-2B-bearing mice compared to controls in vivo (p<0.05). Higher expression of caspase-3 and lower expression of vimentin in PC-3 and C4-2B tumors were induced by vismodegib in immunohistochemical analysis.

CONCLUSION: Vismodegib inhibited cell proliferation via apoptosis and also suppressed EMT, showing anti-tumor effects in mice. Further mechanistic studies are needed to investigate the feasibility of vismodegib for CRPC treatment.

Original languageEnglish
Pages (from-to)5107-5114
Number of pages8
JournalAnticancer Research
Volume40
Issue number9
DOIs
Publication statusPublished - Sep 1 2020

Keywords

  • Castration-resistant prostate cancer
  • Epithelial-mesenchymal transition
  • Hedgehog signaling
  • Sonic hedgehog
  • Vismodegib
  • Immunohistochemistry
  • Hedgehog Proteins/metabolism
  • Humans
  • Immunophenotyping
  • Male
  • Anilides/pharmacology
  • Signal Transduction/drug effects
  • Xenograft Model Antitumor Assays
  • Antineoplastic Agents/pharmacology
  • Animals
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition/drug effects
  • Mice
  • Cell Proliferation/drug effects
  • Prostatic Neoplasms, Castration-Resistant/drug therapy
  • Disease Models, Animal
  • Pyridines/pharmacology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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