Antitumoral activity of rapamycin mediated through inhibition of HIF-1alpha and VEGF in hepatocellular carcinoma.
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.
Wang
Wei
W
Centre for the Study of Liver Cancer, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, People's Republic of China.
Jia
Wei-Dong
WD
Xu
Ge-Liang
GL
Wang
Zhi-Hua
ZH
Li
Jian-Sheng
JS
Ma
Jin-Liang
JL
Ge
Yong-Sheng
YS
Xie
Sheng-Xue
SX
Yu
Ji-Hai
JH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors*; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D000903:Antibiotics, Antineoplastic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D020123:Sirolimus