Anti-tumor effect of hedgehog signaling inhibitor, vismodegib, on castration-resistant prostate cancer

Aya Ishii, Katsumi Shigemura, Koichi Kitagawa, Shian Ying Sung, Kuan Chou Chen, Chiang Yi-Te, Ming Che Liu, Masato Fujisawa

研究成果: 雜誌貢獻文章同行評審

9 引文 斯高帕斯(Scopus)


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.

頁(從 - 到)5107-5114
期刊Anticancer Research
出版狀態已發佈 - 9月 1 2020

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究


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