Int. J. Mol. Sci. 2011, 12(4), 2650-2663; doi:10.3390/ijms12042650
Article

In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)

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Received: 12 February 2011; in revised form: 8 March 2011 / Accepted: 1 April 2011 / Published: 19 April 2011
(This article belongs to the Special Issue Conjugated Polymers)
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Abstract: HM-3, designed by our laboratory, is a polypeptide composed of 18 amino acids. Pharmacodynamic studies in vivo and in vitro indicated that HM-3 could inhibit endothelial cell migration and angiogenesis, thereby inhibiting tumor growth. However, the half-life of HM-3 is short. In this study, we modified HM-3 with different polyethylene glycols (PEG) in order to reduce the plasma clearance rate, extend the half-life in the body, maintain a high concentration of HM-3 in the blood and increase the therapeutic efficiency. HM-3 was modified with four different types of PEG with different molecular weights (ALD-mPEG5k, ALD-mPEG10k, SC-mPEG10k and SC-mPEG20k), resulting in four modified products (ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3, respectively). Anti-tumor activity of these four modified HM-3 was determined in BALB/c mice with Taxol as a positive control and normal saline as a negative control. Tumor weight inhibition rates of mice treated with Taxol, HM-3, ALD-mPEG5k-HM-3, ALD-mPEG10k-HM-3, SC-mPEG10k-HM-3 and SC-mPEG20k-HM-3 were 44.50%, 43.92%, 37.95%, 31.64%, 20.27% and 50.23%, respectively. Tumor inhibition rates in the Taxol, HM-3 and SC-mPEG20k-HM-3 groups were significantly higher than that in the negative control group. The efficiency of tumor inhibition in the SC-mPEG20k-HM-3 group (drug treatment frequency: once per two days) was better than that in the HM-3 group (drug treatment frequency: twice per day). In addition, tumor inhibition rate in the SC-mPEG20k-HM-3 group was higher than that in the taxol group. We conclude that SC-mPEG20k-HM-3 had a low plasma clearance rate and long half-life, resulting in high anti-tumor therapeutic efficacy in vivo. Therefore, SC-mPEG20k-HM-3 could be potentially developed as new anti-tumor drugs.
Keywords: PEG modification; peptides; HM-3; anti-tumor; activities
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Liu, Z.; Ren, Y.; Pan, L.; Xu, H.-M. In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG). Int. J. Mol. Sci. 2011, 12, 2650-2663.

AMA Style

Liu Z, Ren Y, Pan L, Xu H-M. In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG). International Journal of Molecular Sciences. 2011; 12(4):2650-2663.

Chicago/Turabian Style

Liu, Zhendong; Ren, Yinling; Pan, Li; Xu, Han-Mei. 2011. "In Vivo Anti-Tumor Activity of Polypeptide HM-3 Modified by Different Polyethylene Glycols (PEG)." Int. J. Mol. Sci. 12, no. 4: 2650-2663.


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