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.
- Castration-resistant prostate cancer
- Epithelial-mesenchymal transition
- Hedgehog signaling
- Sonic hedgehog
- Hedgehog Proteins/metabolism
- Signal Transduction/drug effects
- Xenograft Model Antitumor Assays
- Antineoplastic Agents/pharmacology
- Cell Line, Tumor
- Epithelial-Mesenchymal Transition/drug effects
- Cell Proliferation/drug effects
- Prostatic Neoplasms, Castration-Resistant/drug therapy
- Disease Models, Animal
ASJC Scopus subject areas
- Cancer Research