[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-337928-105":59,"doc-detail-337928-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","dexamethasonetamoxifen-combination-exerts-synergistic-therapeutic-effects-in-tamoxifen-resistance-breast-cancer-cells","Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells","","Tamoxifen-resistant, estrogen receptor-positive breast cancer remains a major clinical challenge, with roughly 30% of patients relapsing and showing reduced survival due to tamoxifen resistance. This research investigates how combining dexamethasone (DEX) with tamoxifen (TAM) inhibits TAM-resistant LCC-2 cells (TAMR-1) by modulating the E2F3/SOX-2-mediated Wnt signaling pathway. Combination treatment synergistically suppresses proliferation and migration, triggers apoptosis, lowers SOX-2 and E2F3 expression, and induces S and G2-M cell-cycle arrest.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dexamethasonetamoxifen-combination-exerts-synergistic-therapeutic-effects-in-tamoxifen-resistance-breast-cancer-cells/337928/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dexamethasonetamoxifen-combination-exerts-synergistic-therapeutic-effects-in-tamoxifen-resistance-breast-cancer-cells/337928.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What problem does the study address?","Question",{"text":113,"@type":114},"The study targets tamoxifen resistance in estrogen receptor-positive breast cancer, where a substantial portion of patients experience relapse and reduced survival.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did the researchers evaluate the DEX and TAM combination?",{"text":118,"@type":114},"They assessed effects on TAMR-1 and MCF-7 cell viability, analyzed drug interactions using CompuSyn and SynergyFinder, and measured cell cycle, apoptosis-related protein expression, gene expression of SOX-2 and E2F3, and cell migration.",{"name":120,"@type":111,"acceptedAnswer":121},"What mechanism is proposed for overcoming tamoxifen resistance?",{"text":122,"@type":114},"The combination therapy is proposed to modulate the E2F3/SOX-2-mediated Wnt signaling pathway, reducing SOX-2 and E2F3 expression and promoting apoptosis and cell-cycle arrest.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},337928,1790071996,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","Bioscience Reports (2024) 44 BSR20240367 [https://doi.org/10.1042/BSR20240367](https://doi.org/10.1042/BSR20240367)  \nResearch Article  \nDexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells  \nAliaa I. Gaballah1 , Aliaa A. Elsherbiny2 , Marwa Sharaky3 , Najat O. Hamed4 , Nahed A. Raslan5,6 ,  \nAbdullah Almilaibary7 , Reda Mohamed Abdrabbou Fayyad8,9 , Mona S. Ousman10 , Ahmed M.E. Hamdan11 and  \n Sally A. Fahim2  \n1 School of Pharmacy, Newgiza University (NGU), Newgiza, km 22 Cairo-Alexandria Desert Road, Giza, P.O. Box 12577, Egypt; 2 Department of Biochemistry, School of Pharmacy, Newgiza University (NGU), Newgiza, km 22 Cairo-Alexandria Desert Road, Giza, P.O. Box 12577, Egypt; 3 Pharmacology Unit, Department of Cancer Biology, National Cancer Institute, Cairo University, Giza, Egypt; 4 Department of Pharmaceutical Sciences, College of Pharmacy, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia;  \n5 Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11651, Egypt; 6 Clinical Pharmacy Program, College of Health Sciences and Nursing, Al-Rayan Colleges, Medina 42541, Saudi Arabia; 7 Department of Family and Community Medicine, Faculty of Medicine, Al-Baha University, AlBaha, Saudi Arabia; 8 Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 9 Department of Pharmacology, General Medicine Practice Program, Batterjee Medical College, Aseer 61961, Saudi Arabia; 10 Emergency Medical Services, College of Applied Sciences, AlMaarefa University, P.O. Box 71666, Riyadh 11597, Saudi Arabia;  \n11 Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia Correspondence: Sally A. Fahim ([sally.atef@ngu.edu.eg](sally.atef@ngu.edu.eg))  \nReceived: 20 March 2024  \nRevised: 03 June 2024  \nAccepted: 11 June 2024  \nAccepted Manuscript online:  \n12 June 2024  \nVersion of Record published:  \n05 July 2024  \nTamoxifen (TAM) is a key player in estrogen receptor-positive (ER+) breast cancer (BC); however, ∼30% of patients experience relapse and a lower survival rate due to TAM resistance. TAM resistance was related to the over expression of SOX-2 gene, which is regulated by the E2F3 transcription factor in the Wnt signaling pathway. It was suggested that SOX-2 overexpression was suppressed by dexamethasone (DEX), a glucocorticoid commonly prescribed to BC patients. The aim of the present study is to explore the effect of combining DEX and TAM on the inhibition of TAM-resistant LCC-2 cells (TAMR-1) through modulating the E2F3/SOX-2-mediated Wnt signaling pathway. The effect of the combination therapy on MCF-7 and TAMR-1 cell viability was assessed. Drug interactions were analyzed using CompuSyn and SynergyFinder softwares. Cell cycle distribution, apoptotic protein expression, gene expression levels of SOX-2 and E2F3, and cell migration were also assessed. Combining DEX with TAM led to synergistic inhibition of TAMR-1 cell proliferation and migration, induced apoptosis, reduced SOX-2 and E2F3 expression and was also associated with S and G2-M phase arrest. Therefore, combining DEX with TAM may present an effective therapeutic option to overcome TAM resistance, by targeting the E2F3/SOX-2/Wnt signaling pathway, in addition to its anti-inflammatory effect.  \nIntroduction  \nBreast cancer (BC) is the most widely diagnosed cancer globally, with about 2.3 million females diagnosed in 2020 [1] . It also accounted for over 685,000 female deaths, making it the second leading cause of cancer death worldwide [2,3] . Additionally, more than 3 million new cases and 1 million deaths are predicted to occur in 2040 [4] . Similarly, in Egypt, BC was the most diagnosed cancer and the second leading cause of cancer mortality in 2020 [5] .  \nEstrogen is a major player in the development of BC and approximately 80% of cases are estrogen receptor positive (ER+) [6] . The car","cbCaim3v0vL85rU2","https://ap.wps.com/l/cbCaim3v0vL85rU2","pdf",5197634,16,"English","# Introduction\n## Breast cancer and tamoxifen resistance\n## Role of estrogen and endocrine therapy\n## SOX-2, E2F3, and Wnt signaling","[{\"question\":\"What problem does the study address?\",\"answer\":\"The study targets tamoxifen resistance in estrogen receptor-positive breast cancer, where a substantial portion of patients experience relapse and reduced survival.\"},{\"question\":\"How did the researchers evaluate the DEX and TAM combination?\",\"answer\":\"They assessed effects on TAMR-1 and MCF-7 cell viability, analyzed drug interactions using CompuSyn and SynergyFinder, and measured cell cycle, apoptosis-related protein expression, gene expression of SOX-2 and E2F3, and cell migration.\"},{\"question\":\"What mechanism is proposed for overcoming tamoxifen resistance?\",\"answer\":\"The combination therapy is proposed to modulate the E2F3/SOX-2-mediated Wnt signaling pathway, reducing SOX-2 and E2F3 expression and promoting apoptosis and cell-cycle arrest.\"}]","Dexamethasone–tamoxifen combination exerts synergistic therapeutic effects in tamoxifen-resistance breast cancer cells | PDF",1790021216]