title: Sonic hedgehog pathway inhibitor mitigates mouse hepatocellular carcinoma.
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.
  
  
  CONCLUSIONS
  GDC-0449 could effectively mitigate HCC growth in vivo.
authors.affiliation: Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan. Electronic address: kevin.ksjeng@gmail.com.
authors.forename: Kuo-Shyang
authors.initials: KS
authors.lastname: Jeng
authors.affiliation: Department of Ophthalmology, Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chi-Juei
authors.initials: CJ
authors.lastname: Jeng
authors.affiliation: Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Wen-Juei
authors.initials: WJ
authors.lastname: Jeng
authors.affiliation: Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: I-Shyan
authors.initials: IS
authors.lastname: Sheen
authors.affiliation: Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Chiung-Fang
authors.initials: CF
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Hsiau
authors.affiliation: Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Zih-Hang
authors.initials: ZH
authors.lastname: Hung
authors.affiliation: Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Ming-Che
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Department of Medical Research, Far Eastern Memorial Hospital, Taipei, Taiwan.
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Chang
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D015536:Down-Regulation; D015870:Gene Expression; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000071676:Zinc Finger Protein GLI1
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C538724:HhAntag691; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011725:Pyridines; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C465570:Shh protein, mouse; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1
keywords: GDC-0449; Gli-1; Ptch-1; Shh; Smo; Sonic hedgehog pathway