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Fusion protein of adenovirus E4orf4 and human epidermal growth factor inhibits tumor cell growth
Author(s) -
Zhou Yu,
Chen Hong,
Ma XiaoLi,
Xie HaiJun,
Wang CunLin,
Zhang ShengHua,
Wang Xin,
Huang BingRen
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24415
Subject(s) - epidermal growth factor , apoptosis , epidermal growth factor receptor , cell growth , cancer research , biology , fusion protein , microbiology and biotechnology , growth factor , in vivo , growth inhibition , cell , cell culture , receptor , recombinant dna , biochemistry , genetics , gene
Adenovirus early region 4 open reading frame 4 (E4orf4) protein is a novel cell death factor that selectively induces apoptosis in cancer cells. This study evaluated tumor inhibitory effects of a protein made by fusion E4orf4 and human epidermal growth factor (EGF). EGF was used to ensure the selective targeting of EGF receptor (EGFR)‐overexpressing tumor cells. Results showed that EGF‐E4orf4 stimulated EGFR phosphorylation in a time‐ and dose‐dependent manner. Confocal microscopy analysis showed both EGF‐E4orf4 and EGF could be internalized via EGFR but they had different intercellular trafficking pathways. In vitro study showed that EGF‐E4orf4 significantly inhibited the proliferation of BGC823 and i n vivo study showed EGF‐E4orf4 suppressed tumor growth in a dose‐dependent fashion with an inhibition rate of 79% for MDA‐MB‐231 and 49% for BGC 823 ( p < 0.05). No toxic effects were observed in the nude mice with a dose as high as 10 mg/kg of EGF‐E4orf4. These results indicated that EGF‐E4orf4 could be a potential drug for cancer therapy. © 2009 UICC