Authors: WeiZhong Wu HuiChuan Sun YueFang Shen Jie Chen Lu Wang ZhaoYou Tang George Iliakis KangDa Liu
Publish Date: 2004/12/11
Volume: 131, Issue: 3, Pages: 169-178
Abstract
An earlier report demonstrated that interferon alpha IFNα inhibited tumor growth and recurrence in an MHCC97 xenograft model in nude mice by suppressing tumor angiogenesis rather than by inhibiting tumor cell proliferation However the underlying molecular mechanism was not fully elucidated In this study we demonstrated that IFNα 2a could downregulate VEGF expression both in mRNA and in protein levels as well as downregulating HIF1α mRNA expression in MHCC97 cells in vitro A cDNA micro array analysis followed by Northern and Western blot analysis revealed that PI3 kinase and MAP kinase signaling pathways might be inhibited by IFNα 2a Blocking the function of IFNα receptor with a specific peptide could eliminate the inhibitory effects of IFNα 2a on VEGF expression In addition wortmannin and PD098059 respective inhibitors of the PI3 kinase and the MAP kinase signaling pathways when used independently or in combination could also downregulate the VEGF synthesis and secretion in a similar pattern of IFNα 2a These observations may lead to the conclusion that IFNα 2a could suppress VEGF synthesis and secretion by downregulating HIF1α expression via inhibition of the PI3 kinase and/or the MAP kinase signaling pathways
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