Targeting Interleukin-4 Receptor a with Hybrid Peptide for Effective Cancer Therapy

نویسندگان

  • Liying Yang
  • Tomohisa Horibe
  • Masayuki Kohno
  • Mari Haramoto
  • Koji Ohara
  • Raj K. Puri
  • Koji Kawakami
چکیده

Interleukin-4 receptor a (IL-4Ra) chain is highly expressed on the surface of various human solid tumors. We designed a novel hybrid peptide termed IL-4Ra–lytic peptide that targets the IL-4Ra chain. The IL-4Ra–lytic peptide contains a target moiety to bind to IL-4Ra and a cellular toxic lytic peptide that selectively kills cancer cells. The anticancer activity of the IL-4Ra–lytic peptide was evaluated in vitro and in vivo. It was found that the IL-4Ra–lytic peptide has cytotoxic activity in cancer cell lines expressing IL-4Ra, determined by quantitative real-time PCR. The IC50 ratios of the lytic peptide to the IL-4Ra–lytic peptide correlated well with the expression levels of IL-4Ra on cancer cells (r 1⁄4 0.80). In addition, IL-4Ra–lytic peptide administered either intratumoraly or intravenously significantly inhibited tumor growth in xenograft model of human pancreatic cancer (BXPC-3) in mice. These results indicate that the IL-4Ra–lytic peptide generated in this study has a potent and selective anticancer potential against IL-4Ra–positive solid cancers. Mol Cancer Ther; 11(1); 235–43. 2011 AACR.

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تاریخ انتشار 2011