{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:55:21Z","timestamp":1791262521668,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Lung adenocarcinoma (LUAD) continues to present therapeutic challenges because of pathway redundancy and treatment resistance, underscoring the need for multi-target and systems-level strategies. Baicalein (BA), a flavonoid metabolite from\n                      <jats:italic>Scutellaria baicalensis<\/jats:italic>\n                      Georgi, shows antitumor potential, yet integrative and immune-related evaluations of BA in LUAD remain limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We integrated network analyses with TCGA-LUAD transcriptomics, weighted gene co-expression network analysis (WGCNA), network topology, GO\/KEGG enrichment, bulk RNA-seq-based immune-infiltration estimation (CIBERSORT), molecular docking, and clinical association analysis (GEPIA2\/HPA). Cell viability was assessed in A549 cells\u200b using the CCK-8 assay, and AKT1 phosphorylation and BCL2 protein expression were further examined experimentally by western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 117 candidate BA-LUAD overlapping targets were identified, and six candidate hub genes (EGFR, AKT1, TP53, BCL2, HIF1A, and ESR1) were prioritized. Enrichment analyses suggested that the candidate network was associated with oncogenic signaling and stress-response programs, particularly PI3K-AKT\/MAPK signaling, ROS-related processes, apoptosis, and p53 signaling. CCK-8 assays showed that BA reduced A549 cell viability\n                      <jats:italic>in vitro<\/jats:italic>\n                      , with IC\n                      <jats:sub>50<\/jats:sub>\n                      values of 54.93 \u03bcM at 24\u00a0h and 22.83 \u03bcM at 48\u00a0h. Among the prioritized candidates, AKT1 and BCL2 were selected for focused experimental assessment in A549 cells. BA treatment reduced AKT1 phosphorylation and BCL2 protein expression in A549 cells, whereas total AKT1 remained largely unchanged. HIF1A expression showed broad associations with computationally estimated immune-cell fractions and poorer overall survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings prioritize a BA-associated candidate network in LUAD involving kinase signaling, apoptosis-related regulation, oxidative-stress responses, and immune-microenvironment associations. The CCK-8 results support an inhibitory effect of BA on A549 cell viability\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and the observed changes in AKT1 phosphorylation and BCL2 protein expression provide focused experimental support for selected components of the candidate network; further\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      studies are required to validate biological relevance and translational potential.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1912108","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:26:20Z","timestamp":1791260780000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the mechanisms of baicalein in lung adenocarcinoma: an integrative preliminary study with focused experimental assessment in A549 cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Jiaqian","family":"Yuan","sequence":"first","affiliation":[{"name":"The First School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Ningbo TCM Hospital Affiliated to Zhejiang Chinese Medical University","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00312-3","article-title":"Lung 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