[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-373905-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-373905-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","glucocorticoid-inhibits-lung-cancer-cells-proliferation-and-migration-by-suppressing-smad23-activation","Glucocorticoid inhibits lung cancer cells proliferation and migration by suppressing smad2/3 activation","","Dexamethasone (DEX), a glucocorticoid used to alleviate chemotherapy or immunotherapy adverse events in lung cancer, was investigated for direct effects on lung cancer progression. The study assessed DEX-driven changes in A549 and LLC proliferation and migration using EdU, CCK8, Transwell, wound healing, TCGA/HPA analysis, qPCR, and Western blotting, with in vivo tumor models. DEX strongly reduced Smad2/3 activation and associated TGFβ/Smad signaling, limiting tumor cell growth and motility; Smad2/3 activation agonism restored these inhibitory effects, supporting a GR-independent mechanism.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/glucocorticoid-inhibits-lung-cancer-cells-proliferation-and-migration-by-suppressing-smad23-activation/373905/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/glucocorticoid-inhibits-lung-cancer-cells-proliferation-and-migration-by-suppressing-smad23-activation/373905.png","ImageObject",300,407,{"name":42,"@type":43},"LangkahRina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-28","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does the study address about glucocorticoids in lung cancer?","Question",{"text":63,"@type":64},"It tests whether dexamethasone directly affects lung cancer cell proliferation and migration, rather than only reducing treatment-related adverse events.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did DEX influence lung cancer cell proliferation and migration?",{"text":68,"@type":64},"DEX treatment significantly inhibited proliferation and migration in A549 and LLC cells, and reduced related tumor activity in vitro and in vivo.",{"name":70,"@type":61,"acceptedAnswer":71},"What role does Smad2/3 activation play in DEX’s effects?",{"text":72,"@type":64},"DEX suppressed Smad2/3 activation; Smad2/3 knockdown reduced proliferation and migration, while activating Smad2/3 or overexpressing Smad2/3 reversed DEX’s inhibitory effects.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},373905,1790466201,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nGlucocorticoid inhibits lung cancer cells proliferation and migration by suppressing smad2/3 activation  \nLei Xu1,2, Qi Li1,2, Chang Xu1, Dongmei Tan1 & Yi Tan1􀀍  \nGlucocorticoid (GCs), as an adjuvant drug, is widely used for alleviating chemotherapy or immunotherapy-induced adverse events, such as nausea and immune-related diseases in lung cancer treatment. However, whether GCs directly affects lung cancer progression remains unclear. This study focused on the effects of dexamethasone (DEX) on the proliferation and migration of lung cancer cells as well as the related potential mechanisms using EdU, CCK8, Transwell, Wound healing, TCGA database, HPA database, qPCR and Western blotting. Additionally, subcutaneous tumor and tail vein tumor injection models were established for investigating DEX action in vivo. Further, to confirm the key functional of Smad2/3 for DEX regulating lung cancer cells proliferation and migration. Mechanistic assays explored the upstream regulatory molecules TGFβ1, TGFβR1 and p-TGFβR1 expression after DEX treatment. Moreover, DEX modulates lung cancer cell proliferation and migration on a glucocorticoid receptor (GR)-independent manner and the association with Smad2/3 activation were investigated. Results: The results showed that DEX (1 µM) treatment significantly inhibited the proliferation and the migration of lung cancer cells A549 and LLC cells. TCGA and HPA databases showed Smad2/3 expression was positively correlated with lung cancer progression. Mechanistically, DEX treatment significantly inhibited Smad2/3 activation in vitro and in vivo, manifested as a decrease in the expression of p-Smad2 (Ser465/467), Smad2, p-Smad3 (Ser423/425), and Smad3 . Smad2/3 knockdown significantly inhibit the proliferation, migration and Smad2/3 activity of A549 and LLC cells. Creatine, the agonist of Smad2/3 activation, markedly reversed the inhibitory effects of DEX on the proliferation and migration of A549 and LLC cells. Smad2/3 overexpression also reversed the inhibitory effects of DEX onA549 cell proliferation and migration. Further studies showed DEX inhibited the expression ofTGFβR1 and p-TGFβR1(Ser165) and the levels ofTGFβ1 . Moreover, GR knockout significantly promoted the proliferation, migration and Smad2/3 activity inA549 cell. DEX can inhibits A549 cell proliferation and migration through suppressing Smad2/3 activation independent of GR. Conclusion: DEX inhibited the proliferation and migration of lung cancer cells by suppressing Smad2/3 activation, providing a theoretical basis and experimental data for clinical practice.  \nKeywords Dexamethasone, Proliferation, Migration, Lung cancer, Smad2/3 activation, GR independent manner  \nAbbreviations  \nGCs Glucocorticoid  \nDEX Dexamethasone  \nNSCLC Non-small cell lung cancer ICIs Immune checkpoint inhibitors  \nirAEs Immune-related adverse events  \nGCs Glucocorticoid  \nRb Retinoblastoma  \nTGFβ Transforming growth factor-β HE Hematoxylin and eosin  \nR-SMADs Receptor-regulated SMADs  \nTCGA The Cancer Genome Atlas  \nTNM Tumor, node, and metastasis  \nHPA Human Protein Atlas  \n1Laboratory Animal Center, Chongqing Medical University, Chongqing 400016, China. 2Lei Xu and Qi Li these authors contributed equally to this work. 􀀍 email: [tanyee66@cqmu.edu.cn](tanyee66@cqmu.edu.cn)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nIHC Immunohistochemistry  \nELISA Enzyme linked immunosorbent assay  \nLung cancer has the highest global incidence and mortality rates among all cancers, accounting for nearly onefifth of all cancer-related death1,2. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers with a 5-year survival rate of less than 3%3. In clinics, traditional chemotherapy and immunotherapy targeting immune checkpoint inhibitors (ICIs), such as PD1, PDL1, and CTLA4, are used to treat NSCLC patients4. However, chemotherapy can ca","cbCaihYVa5pHwDxW","https://ap.wps.com/l/cbCaihYVa5pHwDxW","pdf",11584888,18,"English","# Background\n## Glucocorticoids in NSCLC treatment\n## TGF-β/Smad signaling in lung cancer\n# Experimental approach\n## In vitro functional assays\n## TCGA and HPA analyses\n## In vivo tumor models\n# Mechanistic findings\n## Smad2/3 activation suppression by DEX\n## Smad2/3 knockdown and rescue experiments\n## GR-independent effects and upstream molecules","[{\"question\":\"What question does the study address about glucocorticoids in lung cancer?\",\"answer\":\"It tests whether dexamethasone directly affects lung cancer cell proliferation and migration, rather than only reducing treatment-related adverse events.\"},{\"question\":\"How did DEX influence lung cancer cell proliferation and migration?\",\"answer\":\"DEX treatment significantly inhibited proliferation and migration in A549 and LLC cells, and reduced related tumor activity in vitro and in vivo.\"},{\"question\":\"What role does Smad2/3 activation play in DEX’s effects?\",\"answer\":\"DEX suppressed Smad2/3 activation; Smad2/3 knockdown reduced proliferation and migration, while activating Smad2/3 or overexpressing Smad2/3 reversed DEX’s inhibitory effects.\"}]","Glucocorticoid inhibits lung cancer cells proliferation and migration by suppressing smad2/3 activation | PDF",1790200779,45]