{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T20:34:28Z","timestamp":1787949268999,"version":"build-2784847793"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972103"],"award-info":[{"award-number":["81972103"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007937","name":"Peking University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007937","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>Osteosarcoma (OS) is the most common malignancy of bone. Liensinine exerts antitumor effects on cancers of the colon, breast, and gallbladder. However, its antitumor activity in OS remains unclear. This study is aimed at investigating the efficacy of liensinine against OS and the underlying mechanism of action. Cell proliferation, apoptosis, and cycle arrest in OS were detected using the Cell Counting Kit\u20108 (CCK\u20108), colony formation, and flow cytometry assays, respectively. The production of reactive oxygen species (ROS), glutathione (GSH) and glutathione disulfide (GSSG) concentrations, and mitochondrial membrane potential (MMP) of OS cells were measured by flow cytometry, colorimetry, and JC\u20101 staining. The expressions of factors related to apoptosis, cell cycle, and activation of the JAK2\/STAT3 pathway were determined by Western blotting. To examine the potential role of ROS, an antioxidant (N\u2010acetyl cysteine, NAC) was used in combination with liensinine. <jats:italic>In vivo<\/jats:italic>, we generated a xenograft mouse model to assess its antitumor efficacy. Tissue level expressions of factors related to apoptosis and activation of the JAK2\/STAT3 pathway were assessed by immunohistochemistry or Western blotting. Liensinine inhibited the proliferation and induced G0\/G1 phase arrest and apoptosis of OS cells in a dose\u2010dependent manner. Additionally, liensinine promoted intracellular ROS production, enhanced the GSSG\/GSH ratio, and induced MMP loss and ROS\u2010mediated suppression of the JAK2\/STAT3 pathway. NAC significantly attenuated the liensinine\u2010induced antitumor activities and activated the JAK2\/STAT3 pathway. <jats:italic>In vivo<\/jats:italic>, liensinine effectively inhibited the OS growth and promoted apoptosis; however, it had no negative effect on the internal organs. In conclusion, liensinine\u2010induced ROS production could suppress the activation of the JAK2\/STAT3 pathway and inhibit the OS growth both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Our findings provided a new rationale for subsequent academic and clinical research on OS treatment.<\/jats:p>","DOI":"10.1155\/2022\/8245614","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T21:35:09Z","timestamp":1643146509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Liensinine Inhibits Osteosarcoma Growth by ROS\u2010Mediated Suppression of the JAK2\/STAT3 Signaling 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