{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T17:37:41Z","timestamp":1793122661828,"version":"4.5.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Jinhua major science and technology project","award":["2023-3-071"],"award-info":[{"award-number":["2023-3-071"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Shikonin (SH) is a natural component extracted from\n                    <jats:italic>Lithospermum erythrorhizon<\/jats:italic>\n                    Siebold &amp; Zucc, a traditional Chinese medicine, which has been shown to have anti-tumor effects in recent years. However, the specific mechanism behind these effects has not yet been reported. Thus, it is important to clarify the specific anti-tumor mechanism of SH and then develop it as a new anti-tumor drug. The objective of this study was to investigate the anti-tumor effect of SH on lung adenocarcinoma and its associated mechanism. SH was co-cultured with A549 cells, and the effects of SH on tumor-related phenotypes were evaluated via methods such as CCK-8, transwell, and TUNEL assays. Transcriptomics was performed to investigate the expression profile of SH-regulated genes as well as the signaling pathways involved. Moreover, the anti-tumor effect of SH was verified using a mouse lung cancer xenograft model. SH inhibited the proliferation, metastasis, and invasion of A549 cells, promoted apoptosis, and regulated the expression of malignant phenotype-related markers. The transcriptomic analysis indicated that SH regulated the expression of various malignant phenotype-related mRNAs and inhibited the Hedgehog pathway activation. Furthermore, SH improved the general state of lung cancer-bearing mice, suppressed the growth of transplanted tumors, and inhibited the expression of tumor markers. The findings of this study are the first to reveal the anti-lung adenocarcinoma effect of SH from multiple perspectives\u2014namely, increasing cancer cell apoptosis and suppressing cancer cell proliferation, metastasis, and invasion by inhibiting the Hedgehog pathway activation.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-28080-9","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T13:11:28Z","timestamp":1766581888000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Shikonin inhibits multiple tumor malignant phenotypes and is associated with Hedgehog pathway downregulation in lung adenocarcinoma"],"prefix":"10.1038","volume":"15","author":[{"given":"Hong-Gang","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Xia","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei-Ling","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Bo","family":"Lou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan-Chao","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Hong","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"issue":"10","key":"28080_CR1","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1002\/cac2.12359","volume":"42","author":"P Chen","year":"2022","unstructured":"Chen, P., Liu, Y., Wen, Y. & Zhou, C. 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