{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T23:14:15Z","timestamp":1767136455709,"version":"build-2238731810"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T00:00:00Z","timestamp":1474502400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473231"],"award-info":[{"award-number":["81473231"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Imatinib (IM), a tyrosine\u2010kinase inhibitor, is used in treatment of multiple cancers, most notably Philadelphia chromosome\u2010positive (Ph\n                      <jats:sup>+<\/jats:sup>\n                      ) chronic myelogenous leukemia (CML). However, the majority of patients continue to present with minimal residual disease occurred in the bone marrow (BM) microenvironment. One of the key factors that contribute to leukemia cell drug resistance is chemokine CXCL12. In the current study, co\u2010culturing CML cell K562 and KU812 with BM stromal cell M2\u201010B4 attenuated IM\u2010induced apoptosis. CXCL12\/CXCR7 pathway was activated in co\u2010culture models, which was further proved to be related to drug resistance by silencing CXCR7. ERK phosphorylation and downstream apoptosis related proteins\u2019 activation were also observed in co\u2010culture group after the activation of CXCR7. Moreover, oroxylin A, a bioactive flavonoid isolated from the root of\n                      <jats:italic>Scutellaria baicalensis Georgi<\/jats:italic>\n                      , was found to be effective in reversing BM stroma induced CML resistance to IM. After cells were treated with weakly toxic concentration of oroxylin A, cell apoptosis induced by IM in co\u2010culture model was enhanced. And the activated CXCL12\/CXCR7 pathway, the expression of p\u2010ERK and downstream apoptosis related proteins were suppressed. The in vivo study also showed that oroxylin A increased apoptosis of CML cells with low systemic toxicity, and the mechanism was consistent with the in vitro study. In conclusion, oroxylin A improved sensitivity of CML cells to IM treatment in BM microenvironment through regulating CXCL12\/CXCR7 pathway. \u00a9 2016 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22540","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T18:42:44Z","timestamp":1471459364000},"page":"863-876","source":"Crossref","is-referenced-by-count":24,"title":["Oroxylin A reverses the drug resistance of chronic myelogenous leukemia cells to imatinib through CXCL12\/CXCR7 axis in bone marrow microenvironment"],"prefix":"10.1002","volume":"56","author":[{"given":"Wenjun","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and Intervention China Pharmaceutical University Nanjing People's Republic of 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