Fusion protein of adenovirus E4orf4 and human epidermal growth factor inhibits tumor cell growth.
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 in 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.
Zhou
Yu
Y
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College, Beijing, China.
Chen
Hong
H
Ma
Xiao-Li
XL
Xie
Hai-Jun
HJ
Wang
Cun-Lin
CL
Zhang
Sheng-Hua
SH
Wang
Xin
X
Huang
Bing-Ren
BR
D000230:Adenocarcinoma / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004815:Epidermal Growth Factor / Q000235:genetics*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D014764:Viral Proteins / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
C121517:E4orf4 protein, adenovirus; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors