Sonic hedgehog pathway inhibitor mitigates mouse hepatocellular carcinoma

Kuo Shyang Jeng, Chi Juei Jeng, Wen Juei Jeng, I. Shyan Sheen, Chiung Fang Chang, Hsin I. Hsiau, Zih Hang Hung, Ming Che Yu, Fang Yu Chang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Background Hepatocellular carcinoma (HCC) is a leading cause of death in Asian countries. Sonic hedgehog (Shh) pathway plays a role in hepatocarcinogenesis. We investigated the treatment effect of mouse HCC with Shh inhibitor GDC-0449. Methods Mouse hepatoma ML-1 cells were implanted in B6 mice. Fifteen days later, GDC-0449 (vismodegib), antagonist of smoothened, was used to treat HCC-bearing mice. The tumor size and liver histopathological features were analyzed, as well as gene expression in Shh pathways. Results GDC-0449 treatment effectively reduced tumor size and cell infiltration of the HCC in mice. Gene expression of Shh pathway molecules was altered, including upregulated Shh expression and downregulated smoothened expression in tumor fractions after GDC-0449 treatment. Conclusion GDC-0449 could effectively mitigate HCC growth in vivo.

Original languageEnglish
Pages (from-to)554-560
Number of pages7
JournalAmerican Journal of Surgery
Volume210
Issue number3
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Keywords

  • GDC-0449
  • Gli-1
  • Ptch-1
  • Shh
  • Smo
  • Sonic hedgehog pathway

ASJC Scopus subject areas

  • Surgery

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