Digestive Diseases and Sciences

, Volume 54, Issue 10, pp 2128–2136 | Cite as

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

  • Wei Wang
  • Wei-Dong Jia
  • Ge-Liang Xu
  • Zhi-Hua Wang
  • Jian-Sheng Li
  • Jin-Liang Ma
  • Yong-Sheng Ge
  • Sheng-Xue Xie
  • Ji-Hai Yu
Original Article


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.


Rapamycin Hepatocellular carcinoma HIF-1alpha VEGF Angiogenesis 



Cyclosporine A




Hepatocellular carcinoma


Haematoxylin and eosin


Hypoxia-inducible factor 1 alpha


Mammalian target of rapamycin


Microvessel density








Vascular endothelial growth factor



This research was supported by the National Natural Science Foundation of China (30772097), Anhui Provincial Natural Science Foundation (070413073), the Science and Technological Fund of Anhui Province for Outstanding Youth (08040106818), the Science and Technology Key Project of Anhui Province (07010302193), and the Anhui Provincial “115” Industrial Innovation Program. The authors declare no competing financial interests.


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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Wei Wang
    • 1
    • 2
  • Wei-Dong Jia
    • 1
    • 2
  • Ge-Liang Xu
    • 1
    • 2
  • Zhi-Hua Wang
    • 3
  • Jian-Sheng Li
    • 1
    • 2
  • Jin-Liang Ma
    • 1
    • 2
  • Yong-Sheng Ge
    • 1
    • 2
  • Sheng-Xue Xie
    • 1
  • Ji-Hai Yu
    • 1
    • 2
  1. 1.Centre for the Study of Liver Cancer, Anhui Provincial HospitalAnhui Medical UniversityHefeiPeople’s Republic of China
  2. 2.Department of Hepatic Surgery, Anhui Provincial HospitalAnhui Medical UniversityHefeiPeople’s Republic of China
  3. 3.Department of Pathology, Anhui Provincial HospitalAnhui Medical UniversityHefeiPeople’s Republic of China

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