{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:01:17Z","timestamp":1787061677597,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T00:00:00Z","timestamp":1700352000000},"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","award":["81460255"],"award-info":[{"award-number":["81460255"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81960305"],"award-info":[{"award-number":["81960305"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor angiogenesis is critical for tumor metastasis by providing oxygen, nutrients, and metastatic pathways. As a potential anti\u2010angiogenic agent, Dihydroartemisinin (DHA) can effectively inhibit tumor metastasis. However, the mechanism how it regulates angiogenesis to affect tumor metastasis has not been fully clarified. To investigate the mechanisms of how DHA regulates melanoma progression. In this study, bioinformatics methods were used to analyze the correlation between angiogenesis and melanoma metastasis. Then, B16F10, A375, HUVECs and mouse metastasis models were adapted to clarify the inhibition of DHA in melanoma. GESA analysis revealed melanoma metastasis significantly positive correlated with angiogenesis. Meanwhile, DHA significantly decreased melanoma nodules and lung wet weight in metastatic tumor mice, and inhibited the expression of the angiogenic marker CD31 in vitro and in vivo. Similarly, DHA inhibited the expression of the angiogenic signal molecule VEGFR2 in A375 and B16F10 cells, and significantly suppressed the formation of their tubular structures. DHA\u2010treated supernatants significantly inhibited the tubule\u2010forming ability as well as lateral and longitudinal migration ability of HUVECs compared with untreated melanoma cell supernatants. Screening yielded the angiogenic pathways HIF\u20101\u03b1\/VEGF, PI3K\/ATK\/mTOR associated with melanoma metastasis, and DHA may inhibit tumor metastasis by inhibiting these angiogenic pathways in melanoma cells to inhibit tumor metastasis. Further non\u2010targeted metabolomics analysis revealed that DHA\u2010treated model mice produced differential metabolites that were also associated with angiogenic pathways. DHA inhibits melanoma invasion and metastasis by mediating angiogenesis. These results have important implications for the potential use of DHA in treatment of melanoma.<\/jats:p>","DOI":"10.1002\/ptr.8065","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:52:51Z","timestamp":1700441571000},"page":"1679-1693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Dihydroartemisinin inhibits melanoma migration and metastasis by affecting angiogenesis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8255-433X","authenticated-orcid":false,"given":"Zhaoxiang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Graduate School of Medicine Osaka University, Laboratory of Cutaneous Immunology, Osaka UniversityImmunology Frontier Research Center  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4371-8277","authenticated-orcid":false,"given":"Guihua","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogenic Biology Yanbian University Medical College  Yanji China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2019.7141"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2018.04.018"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-019-1461-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036374"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S249046"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-017-0058-9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.06.015"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-021-01926-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.50364"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2017.02.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-021-00827-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.01.006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104903"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2009.02.003"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.3653"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1655"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14030502"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2012.06.004"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13194987"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94674"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6273"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2022.01.001"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12010033"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.704481"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00858-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdn368"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111873"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.754645"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160596"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.8b00700"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12585"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.720777"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04871"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904059"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104584"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-1855"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.02.002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21654"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06981-w"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.07.024"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.57167"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2022.04.005"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1028647"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07308-5"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1603840113"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21771"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2020.08.001"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-017-0531-3"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.113771"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.727275"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-019-9550-4"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.8065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T12:52:38Z","timestamp":1745326358000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.8065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,19]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1002\/ptr.8065"],"URL":"https:\/\/doi.org\/10.1002\/ptr.8065","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,19]]},"assertion":[{"value":"2023-08-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-10-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}