{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T15:14:14Z","timestamp":1761664454386,"version":"3.40.5"},"reference-count":20,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Immunology Research"],"published-print":{"date-parts":[[2022,4,28]]},"abstract":"<jats:p>Chronic myelocytic leukemia (CML) is a frequently encountered type of leukemia in China. Hypoxia-inducible factor 1 (HIF-1) serves as one of the most important factors of oxygen balance transcription. The activation of this gene mostly marks a poor outlook for cancer patients. To clarify the therapeutic effect of inhibiting this gene on CML, the present study is aimed at exploring the treatment effects of 2-methoxyestradiol (2-ME2), dasatinib alone, and combined both on K-562 cells and the possible mechanism of 2-ME2 in treating the disorder. The levels of HIF-1\u03b1, vascular endothelial growth factor (VEGF), and glutamate synthase 1 (GLU1) genes in K-562 cells were affected dose-dependently after 2-ME2 administration. 2-ME2 induced cell apoptosis by downregulating antiapoptotic protein expressions of Bcl-xl and Bcl-2. The therapeutic effect of single 2-ME2 was superior to single dasatinib, and the effect of combined therapy of both drugs produced better effectiveness than either of the single drug. Once the concentration of 2-ME2 exceeded 0.5\u2009\u03bcM, downregulated C-myc gene expression could exert roles in anti-CML cell proliferation and inducing apoptosis. Dasatinib might participate in the inhibition of the C-myc pathway during this process whereas its effect remained not clear. Taken together, abnormal high expression of HIF-1\u03b1 exerted an essential role in CML occurrence and development. Inhibition of this gene could markedly increase cell apoptosis in a dose-dependent fashion. Moreover, 2-ME2 could induce cell apoptosis by downregulating the C-myc gene and exert an apoptotic effect by downregulating Bcl-xl and Bcl-2 which act as antiapoptotic proteins.<\/jats:p>","DOI":"10.1155\/2022\/6324326","type":"journal-article","created":{"date-parts":[[2022,4,29]],"date-time":"2022-04-29T03:37:14Z","timestamp":1651203434000},"page":"1-11","source":"Crossref","is-referenced-by-count":4,"title":["Combined Effects of 2-Methoxyestradiol (Hypoxia-Inducible Factor 1\u03b1 Inhibitor) and Dasatinib (A Second-Generation Tyrosine Kinase Inhibitor) on Chronic Myelocytic Leukemia Cells"],"prefix":"10.1155","volume":"2022","author":[{"given":"Yuexian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hematology, Wuxi Branch of Ruijin Hospital, Wuxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Wuxi People\u2019s Hospital, Wuxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunfeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Wuxi People\u2019s Hospital, Wuxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9306-0162","authenticated-orcid":true,"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Wuxi People\u2019s Hospital, Wuxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.19746\/j.cnki.issn.1009-2137.2020.05.007"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.675811"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.2016.1133582"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-160603"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.09.027"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2016.11.014"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1038\/s41388-018-0151-1"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2016.1177679"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2330-1"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-0052"},{"issue":"5","key":"11","first-page":"356","article-title":"Omacetaxine mepesuccinate--a semisynthetic formulation of the natural antitumoral alkaloid homoharringtonine, for chronic myelocytic leukemia and other myeloid malignancies","volume":"11","author":"A. 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