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Recent research showed that the truncated \u201creceptorless\u201d <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content> was still capable of being internalized into cells. This study investigated the effects and potential mechanisms of <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup>, a truncated \u201creceptorless\u201d <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content>, on the permeability of the blood\u2013tumor barrier (<jats:styled-content style=\"fixed-case\">BTB<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">BTB<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GEC<\/jats:styled-content>s were subjected to <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> treatment. <jats:styled-content style=\"fixed-case\">HRP<\/jats:styled-content> flux assays, immunofluorescent, co\u2010immunoprecipitation, Western blot, <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>\u20108, and Flow cytometry analysis were used to evaluate the effects of <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed that 5 <jats:italic>\u03bc<\/jats:italic>M of <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> significantly increased the permeability of <jats:styled-content style=\"fixed-case\">BTB<\/jats:styled-content><jats:italic>in vitro<\/jats:italic>, which reached its peak at 6 h. The permeability was reduced by pretreatment with filipinIII. <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> co\u2010localized and interacted with caveolin\u20101 via its caveolin\u2010binding motif. The <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> and protein expression levels of caveolin\u20101 were identical with the changes of <jats:styled-content style=\"fixed-case\">BTB<\/jats:styled-content> permeability. The upregulated expression of caveolin\u20101 was associated with Src kinase\u2010dependent tyrosine phosphorylation of caveolin\u20101, which subsequently induced phosphorylation and inactivation of the transcription factor Egr\u20101. The combination of <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> with doxorubicin significantly enhanced the loss of cell viability and apoptosis of U87 glioma cells in contrast to doxorubicin alone. Conclusions: <jats:styled-content style=\"fixed-case\">DT<\/jats:styled-content><jats:sup>270\u2010326<\/jats:sup> might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the <jats:styled-content style=\"fixed-case\">BTB<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12519","type":"journal-article","created":{"date-parts":[[2016,2,10]],"date-time":"2016-02-10T10:54:55Z","timestamp":1455101695000},"page":"477-487","source":"Crossref","is-referenced-by-count":9,"title":["<scp>DT<\/scp><sup>270\u2010326<\/sup>, a Truncated Diphtheria Toxin, Increases Blood\u2013Tumor Barrier Permeability by Upregulating the Expression of Caveolin\u20101"],"prefix":"10.1111","volume":"22","author":[{"given":"Yang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurobiology College of Basic Medicine China Medical University Shenyang China"},{"name":"Institute of Pathology and Pathophysiology China Medical University 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