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• W2561586883 startingPage "1395" @default.
• W2561586883 abstract "CD13 is a marker of angiogenic endothelial cells, and recently it is proved to be a biomarker of human liver cancer stem cells (CSCs). Herein, the therapeutic effects of NGR‐LDP‐AE, a fusion protein composed of CD13‐targeting peptide NGR and antitumor antibiotic lidamycin, on human liver cancer and its mechanism were studied. Western blot and immunofluorescence assay demonstrated that CD13 (WM15 epitope) was expressed in both human liver cancer cell lines and vascular endothelial cells, while absent in normal liver cells. MTT assay showed that NGR‐LDP‐AE displayed potent cytotoxicity to cultured tumor cell lines with IC 50 values at low nanomolar level. NGR‐LDP‐AE inhibited tumorsphere formation of liver cancer cells, and the IC 50 values were much lower than that in MTT assay, indicating selectively killing of CSCs. In endothelial tube formation assay, NGR‐LDP‐AE at low cytotoxic dose significantly inhibited the formation of intact tube networks. Animal experiment demonstrated that NGR‐LDP‐AE inhibited the growth of human liver cancer xenograft. Immunohistochemical analysis showed that NGR‐LDP‐AE induced the down‐regulation of CD13. In vitro experiment using cultured tumor cells also confirmed this result. NGR‐LDP‐AE activated both apoptotic and autophagic pathways in cultured tumor cells, while the induced autophagy protected cells from death. Conclusively, NGR‐LDP‐AE exerts its antitumor activity via killing liver CSCs and inhibiting angiogenesis. With one targeting motif, NGR‐LDP‐AE acts on both liver CSCs and angiogenic endothelial cells. It is a promising dual targeting fusion protein for liver cancer therapy, especially for advanced or relapsed cancers." @default.
• W2561586883 created "2017-01-06" @default.
• W2561586883 creator A5014334354 @default.
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• W2561586883 date "2017-01-04" @default.
• W2561586883 modified "2023-10-17" @default.
• W2561586883 title "A CD13‐targeting peptide integrated protein inhibits human liver cancer growth by killing cancer stem cells and suppressing angiogenesis" @default.
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• W2561586883 doi "https://doi.org/10.1002/mc.22600" @default.
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• W2561586883 hasPublicationYear "2017" @default.
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