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Journal of Biochemistry Advance Access published online on July 14, 2006
Journal of Biochemistry, doi:10.1093/jb/mvj152
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© 2006 The Japanese Biochemical Society.
Received May 23, 2006
Accepted July 6, 2006

Regular Paper

NGR Enhanced the Anti-Angiogenic Activity of tum-5

Jieru Meng 1 *, Nan Ma 1 *, Zhen Yan 1, Wei Han 1 *, and Yingqi Zhang 1

1 Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, People's Republic of China; State Key Laboratory of Cancer Biology, 17 Changle West Road, 710032 Xi'an, People's Republic of China

* To whom correspondence should be addressed.
Wei Han, E-mail: hanwwcn{at}yahoo.com.cn


  Abstract

Tumstatin is an angiogenesis inhibitor. The anti-angiogenic activity of tumstatin is localized to the 54-132-amino acid. NGR motif is a marker of angiogenic endothelial cells. We synthesized the gene fragment encoding the amino acids 45-132 of tumstatin (tum-5) and coupled a NGR (CNGRCVSGCAGRC) motif to the C-terminal of tum-5 (tum-5-NGR). The both were inserted into pQE30 expression vector and expressed in E. coli. The anti-angiogenic effects of tum-5-NGR and tum-5 were examined in vivo. The results demonstrated the effect of the former was more significant than the latter. After S180 murine cancer xenografts in BALB/C mice were treated with tum-5-NGR or tum-5, tum-5-NGR displayed more significant tumor growth inhibition than tum-5. Binding of tum-5-NGR to normal and tumor tissues was also evaluated. The results showed that the accumulation of tum-5-NGR in tumor tissue was much more than in normal tissues. These data suggest that NGR enhance the anti-angiogenic activity of tum-5.

Keywords: tumstatin; NGR motif; anti-angiogenic effect; tumor growth inhibition; anticancer drug.
* These authors contributed equally to this article
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