Therapeutic efficacy of Vitamin D in experimental c-met-b-catenin-driven hepatocellular cancer

Akiko Matsuda, Kaori Ishiguro, Irene K. Yan, Tushar Patel

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Aberrant activation of b-catenin signaling is frequently observed in hepatocellular cancer. Although Wnt/ b-catenin signaling can be targeted by vitamin D, therapeutic use of vitamin D for this purpose is not currently established. We evaluated the therapeutic use of vitamin D or its analogs using a synthetic transgenic mouse of hepatocarcinogenesis induced by mutant b-catenin, and MET overexpression in which 75% of mice develop well-differentiated HCC within 8 weeks in the absence of fibrosis. Vitamin D receptor expression was similar in both tumoral and nontumoral tissue. There was no significant difference in overall survival, or in tumor progression assessed by imaging, biochemical, or tumor cell burden assessments in mice receiving a vitamin D-supplemented diet containing 12.0 IU VD/g (HVD) compared with a standard diet (SD) containing 2.3 IU VD/g. Furthermore, systemic treatment with calcitriol [vitamin D analog 1a,25(OH)2D3] or EB1089 (synthetic vitamin D analog) by intraperitoneal injection for 4 weeks prolonged median survival but did not increase overall survival compared with controls. Although tumor formation was delayed in males compared with that in females, there was no difference in overall survival between males and females. In conclusion, although 1a,25(OH)2D3 is reported to inhibit b-catenin signaling, as well as proliferation, migration, and differentiation in cancer cells, neither dietary supplementation with vitamin D nor treatment with vitamin D analogs altered the formation or growth of HCC associated with b-catenin activation. These results conclusively demonstrate the lack of utility of targeting vitamin D for therapy of HCC in this setting.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalGene Expression The Journal of Liver Research
Issue number2
StatePublished - 2019


  • Calcitriol
  • Hepatocellular carcinoma (HCC)
  • Hepatocyte growth factor
  • Liver cancer
  • Vitamin D

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics


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