{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:38:03Z","timestamp":1787243883742,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T00:00:00Z","timestamp":1567555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Medical Reward Foundation","award":["YXJL-2018-0164-0026"],"award-info":[{"award-number":["YXJL-2018-0164-0026"]}]},{"name":"National 13th Five-Year Major New Drug Creation Project","award":["2016ZX09191005"],"award-info":[{"award-number":["2016ZX09191005"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Thoracic Cancer"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The aim of this study was to investigate the feasibility of using a combination of apatinib in the treatment of non\u2010small cell lung cancer. Apatinib is a tyrosine kinase inhibitor which selectivelyacts on vascular endothelial growth factor receptor 2 (VEGFR\u20102) and has shown good efficacy in a variety of malignancies, but the drug resistance is fast in single drug therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The inhibitory effect of apatinib and other drugs on lung cancer cells was determined by CCK\u20108 test in vitro, and the IC50 value was determined. To establish a nude mouse xenograft model, observe the inhibitory effect of apatinib combined with other drugs on lung cancer xenografts in nude mice; immunohistochemical staining of tumor microvessel density and Ki67 expression in transplanted tumor tissues; Western blot analysis of related signaling pathways expression; immunohistochemistry was used to detect tumor microvessel density in other organs and to observe its safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this study, we found apatinib combined with pemetrexed, the first and third generation of epidermal growth factor receptor tyrosine kinase inhibitor, could synergistically inhibit the proliferation of non\u2010small cell lung cancer cell (NSCLC) lines, reduce the microvessel density and Ki67 protein levels of three non\u2010small cell lung cancer xenografts, and enhance anti\u2010tumor activity by synergistically inhibiting the MAPK\u2010ERK and PI3K\u2010AKT\u2010mTOR signaling pathway. Furthermore, there were no pathological abnormalities in the heart, brain, liver and kidney of each group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The efficacy of apatinib combination is better than that of monotherapy, and there is no significant difference in toxicity of important organs, which suggests the feasibility of a combination of apatinib in the treatment of non\u2010small cell lung cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1759-7714.13162","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T23:30:57Z","timestamp":1567639857000},"page":"1868-1878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The effect of apatinib combined with chemotherapy or targeted therapy on non\u2010small cell lung cancer in vitro and 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