Digestive Diseases and Sciences

, Volume 54, Issue 10, pp 2128–2136

Antitumoral Activity of Rapamycin Mediated Through Inhibition of HIF-1alpha and VEGF in Hepatocellular Carcinoma

Authors

  • Wei Wang
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
  • Wei-Dong Jia
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
  • Zhi-Hua Wang
    • Department of Pathology, Anhui Provincial HospitalAnhui Medical University
  • Jian-Sheng Li
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
  • Jin-Liang Ma
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
  • Yong-Sheng Ge
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
  • Sheng-Xue Xie
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
  • Ji-Hai Yu
    • Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical University
    • Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical University
Original Article

DOI: 10.1007/s10620-008-0605-3

Cite this article as:
Wang, W., Jia, W., Xu, G. et al. Dig Dis Sci (2009) 54: 2128. doi:10.1007/s10620-008-0605-3

Abstract

Rapamycin (RAPA) inhibits tumor growth and angiogenesis in hepatocellular carcinoma (HCC). The molecular mechanism underlying the antitumoral effects of RAPA remains unclear. Here we established a chemical-induced rat HCC model to investigate the signaling pathways mediating RAPA’s antitumor activity. We found that RAPA exposure significantly diminished tumor growth, angiogenesis, and metastasis of HCC. Meanwhile, the antitumor drug dramatically decreased expression of HIF-1alpha and VEGF, either at mRNA or protein levels. Moreover, the low-dose of RAPA (1.5 mg/kg/day) was effective enough to markedly inhibit tumor progression of HCC. The preliminary results suggested that the antitumoral effects of RAPA might be at least partially mediated through downregulation of HIF-1alpha and VEGF, and low-dose RAPA-based regimens exhibited a promising future in treatment of HCC.

Keywords

RapamycinHepatocellular carcinomaHIF-1alphaVEGFAngiogenesis

Abbreviations

CsA

Cyclosporine A

DEN

Diethylnitrosamine

HCC

Hepatocellular carcinoma

HE

Haematoxylin and eosin

HIF-1alpha

Hypoxia-inducible factor 1 alpha

mTOR

Mammalian target of rapamycin

MVD

Microvessel density

NMOR

N-nitrosomorpholine

RAPA

Rapamycin

SD

Spreque–Dawley

VEGF

Vascular endothelial growth factor

Copyright information

© Springer Science+Business Media, LLC 2008