{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:57:24Z","timestamp":1787507844347,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:00:00Z","timestamp":1658361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pazopanib is an approved multitarget anticancer agent for soft tissue sarcoma (STS) and renal cell carcinoma (RCC), which is also under clinical investigation for other malignancies, including small cell lung cancer (SCLC). However, the potential anti\u2010SCLC mechanisms of pazopanib remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cell viability was evaluated by CCK\u20108, apoptotic cell detection was conducted using annexin V\/PI staining followed by flow cytometry, and Western blot analysis was used to detect the apoptotic\u2010related molecules and ER\u2010stress pathway effectors. The intracellular reactive oxygen species (ROS) level was determined by DCFH\u2010HA staining followed by flow cytometry. An NCI\u2010H446 xenograft model was established to evaluate pazopanib on tumor suppression in vivo. Immunohistochemistry (IHC) was used to assess the proliferative activity of xenograft in NCI\u2010H446 cell\u2010bearing NOD\u2010SCID mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Pazopanib dose\u2010 and time\u2010dependently inhibited SCLC cell proliferation induced significant apoptosis in SCLC cell lines, increased cleaved\u2010caspase3 and Bax, and decreased Bcl\u20102. Moreover, the PERK\u2010related ER\u2010stress pathway was potently activated by pazopanib treatment, inhibiting ER\u2010stress by salubrinal significantly reversing pazopanib\u2010mediated apoptosis in SCLC cell lines. Furthermore, pazopanib\u2010induced intracellular ROS levels increased, while inhibiting ROS by NAC significantly reversed pazopanib\u2010induced apoptosis in SCLC cells. In addition, pazopanib significantly suppressed NCI\u2010H446 xenograft growth and decreased Ki67 positive cells in the tumor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings indicate that pazopanib induces SCLC cell apoptosis through the ER\u2010stress process via upregulation of ROS levels. Further investigation of relevant biomarkers to accurately select patients for benefit from pazopanib should be further investigated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.14543","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T02:41:53Z","timestamp":1658457713000},"page":"2421-2428","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pazopanib restricts small cell lung cancer proliferation via reactive oxygen\n                    <scp>species\u2010mediated<\/scp>\n                    endoplasmic reticulum stress"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7507-4851","authenticated-orcid":false,"given":"Yue","family":"Li","sequence":"first","affiliation":[{"name":"Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory 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