A novel NGR-conjugated peptide targets DNA damage responses for radiosensitization

Author(s): Jinlu Ma, Dan Zhang, Xia Ying, Ying Zhao, Chenchen He, Qing Zhu, Suxia Han

Journal Name: Current Cancer Drug Targets

Volume 15 , Issue 6 , 2015

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Radiotherapy is one of the important treatment strategies for patients with advanced hepatocellular carcinomas. Developing novel sensitizers for radiotherapy is a key issue due to the low intrinsic radiosensitivity of hepatocellular carcinomas. It was reported the wild-type NBS1 inhibitory peptide (wtNIP) can increase radiosensitivity in several cancer cell lines by abrogating ATM-NBS1 interaction and interrupting cellular DNA damage response. Here, we developed a novel NGRconjugated peptide (NGR-sR9-wtNIP) through coupling the CNGRC angiogenic vessel-homing peptide NGR with the wtNIP peptide. Fusion peptide was tested for internalization, cytotoxicity in Hep3B cells and for tumor localization, and for toxicity in nude mice bearing human hepatocellular carcinomas xenografts. The radiosensitizing activity of NGR-sR9-wtNIP was investigated as well. We found that NGR-sR9-wtNIP can inhibit irradiation induced NBS1 phosphorylation and induce radiosensitization in Hep3B cells. When combined with IR, NGR-sR9-wtNIP suppressed tumor growth obviously in xenograft mice. In addition, the fusion peptide localized in tumor tissue specifically and barely led to any side effects on mice. Taken together, our data strongly suggest that NGRsR9- wtNIP has radiosensitizing potential for radiotherapy of hepatocellular carcinomas.

Keywords: DNA damage responses, NGR, irradiation, NIP (NBS1 inhibitory peptide), radiosensitization.

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Article Details

Year: 2015
Page: [533 - 541]
Pages: 9
DOI: 10.2174/1568009615666150408114817
Price: $65

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