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- Title
Antitumoral activity of rapamycin mediated through inhibition of HIF-1alpha and VEGF in hepatocellular carcinoma.
- Authors
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; Wang, Wei; Jia, Wei-Dong; Xu, Ge-Liang; Wang, Zhi-Hua; Li, Jian-Sheng; Ma, Jin-Liang; Ge, Yong-Sheng; Xie, Sheng-Xue; Yu, Ji-Hai
- 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.
- Subjects
RAPAMYCIN; LIVER cancer; TUMOR growth; NEOVASCULARIZATION; MESSENGER RNA; VASCULAR endothelial growth factor antagonists; ANIMAL experimentation; ANTINEOPLASTIC antibiotics; CELLULAR signal transduction; COMPARATIVE studies; ENZYME-linked immunosorbent assay; HEPATOCELLULAR carcinoma; IMMUNOHISTOCHEMISTRY; LIVER tumors; RESEARCH methodology; MEDICAL cooperation; POLYMERASE chain reaction; PROTEINS; RATS; RESEARCH; WESTERN immunoblotting; EVALUATION research; REVERSE transcriptase polymerase chain reaction; PATHOLOGIC neovascularization; CHEMICAL inhibitors; PHARMACODYNAMICS; THERAPEUTICS
- Publication
Digestive Diseases & Sciences, 2009, Vol 54, Issue 10, p2128
- ISSN
0163-2116
- Publication type
journal article
- DOI
10.1007/s10620-008-0605-3