{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:28:52Z","timestamp":1790220532679,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,23]],"date-time":"2012-12-23T00:00:00Z","timestamp":1356220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p>The aim of the present study was to analyse the antiproliferative effects and mechanisms of action of protein kinase inhibitors (<jats:styled-content style=\"fixed-case\">PKI<\/jats:styled-content>s) in human glioblastoma multiforme (<jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content>) cells with different epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) and phosphatase and tensin homologue (<jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content><jats:italic>)<\/jats:italic> status.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content> cell models were established by transfection of plasmids carrying wild\u2010type <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>, mutated <jats:italic><jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>v<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content><\/jats:italic> or <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content> and clonal selection in U87<jats:styled-content style=\"fixed-case\">MG<\/jats:styled-content> cells. Phosphatidylinositol 3\u2010kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3\u2010K)\/<jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content> pathway\u2010focused gene profiles were examined by real\u2010time polymerase chain reaction\u2010based assays, protein expression was evaluated by western blotting and the antiproliferative effects of <jats:styled-content style=\"fixed-case\">PKI<\/jats:styled-content> treatment were determined by the 3\u2010(4,5\u2010dimethyl\u20102 thiazoyl)\u20102,5\u2010diphenyl\u20102H\u2010tetrazolium bromide (<jats:styled-content style=\"fixed-case\">MTT<\/jats:styled-content>) assay in <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content> cells.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The cell model with intact PTEN and low EGFR levels was the most sensitive to treatment with the EGFR inhibitor erlotinib, whereas the model with EGFR<jats:italic>vIII<\/jats:italic> was the most resistant to treatment with the mitogen\u2010activated protein kinase kinase inhibitor U0126. The dual PI3\u2010K and mammalian target of rapamycin (<jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>) inhibitor PI103 had the most potent antiproliferative effects against all GBM cells tested. Following simultaneous stimulation of AKT and extracellular signal\u2010regulated kinase, rapamycin concentrations &gt;\u00a00.5\u00a0nmol\/L failed to exhibit a further growth inhibitory effect. Concurrent inhibition of <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content> and ribosomal protein s6 activity may underlie the inhibition of GBM proliferation by PKI.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>In conclusion, overexpression of <jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content> or <jats:italic><jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>v<jats:styled-content style=\"fixed-case\">III<\/jats:styled-content><\/jats:italic>, accompanied by a loss of <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>, contributed to the activation of multiple intracellular signalling pathways in <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content> cells. Rigorous examination of biomarkers in tumour tissues before and after treatment may be necessary to determine the efficacy of <jats:styled-content style=\"fixed-case\">PKI<\/jats:styled-content> therapy in patients with <jats:styled-content style=\"fixed-case\">GBM<\/jats:styled-content>.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12026","type":"journal-article","created":{"date-parts":[[2012,10,30]],"date-time":"2012-10-30T08:41:27Z","timestamp":1351586487000},"page":"13-21","source":"Crossref","is-referenced-by-count":15,"title":["Effects of epidermal growth factor receptor and phosphatase and tensin homologue gene expression on the inhibition of U87<scp>MG<\/scp> glioblastoma cell proliferation induced by protein kinase inhibitors"],"prefix":"10.1111","volume":"40","author":[{"given":"Wen\u2010Jing","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Immunology Harbin Medical University Harbin China"},{"name":"Immunity and Infection Key Laboratory of Heilongjiang Province Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Immunology Harbin Medical University Harbin China"},{"name":"Immunity and Infection Key Laboratory of Heilongjiang Province Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing\u2010Lian","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Immunology Harbin Medical University Harbin China"},{"name":"Immunity and Infection Key Laboratory of Heilongjiang Province Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Cui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Immunology Harbin Medical University Harbin China"},{"name":"Immunity and Infection Key Laboratory of Heilongjiang Province 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