{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:02:11Z","timestamp":1774069331401,"version":"3.50.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T00:00:00Z","timestamp":1717977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Gansu province natural science foundation","doi-asserted-by":"crossref","award":["21JR7RA394"],"award-info":[{"award-number":["21JR7RA394"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82360029"],"award-info":[{"award-number":["82360029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Gansu province science and technology plan project","award":["21JR7RA435"],"award-info":[{"award-number":["21JR7RA435"]}]},{"name":"Lanzhou University Cui Yin Xue Zi project","award":["CYXZ2023-38"],"award-info":[{"award-number":["CYXZ2023-38"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Imatinib (IM) resistant K562\/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using monodansylcadaverine (MDC) staining. In the K562\/IM mice model, non-obese diabetic severe combined immunodeficent (NOD-SCID) mice were subcutaneously inoculated with K562\/IM cells. After 17\u00a0days of lycorine injection, assessments included tumor size, hematoxylin\u2013eosin (HE) staining, and Ki67 expression.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>After 72\u00a0h of IM treatment, K562\/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24\u00a0h inhibited cell proliferation and induced G0\/G1 phase cell cycle arrest and apoptosis in both K562 and K562\/IM cells. MDC staining indicated reduced autophagy in K562\/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562\/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>In summary, K562\/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562\/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12672-024-01080-3","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T11:02:06Z","timestamp":1718017326000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lycorine attenuated proliferation and induced apoptosis on imatinib-resistant K562 cell by inhibiting autophagy"],"prefix":"10.1007","volume":"15","author":[{"given":"Jun","family":"Bai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuxi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaqiong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liansheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,6,10]]},"reference":[{"issue":"10314","key":"1080_CR1","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1016\/S0140-6736(21)01204-6","volume":"398","author":"J Cortes","year":"2021","unstructured":"Cortes J, Pavlovsky C, Saussele S. 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All animal studies were performed following the recommendations in the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health. The maximal tumor size\/burden permitted by our ethics committee\/IRB is a volume not exceeding a maximum diameter of 2.0\u00a0cm, to ensure the welfare and humane treatment of the animal subjects involved in the study. We confirm that the maximal tumor size\/burden in this study was not exceeded in any of the animal subjects used in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No application.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"217"}}