{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T20:28:49Z","timestamp":1786566529988,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006662","name":"Ardabil University of Medical Sciences","doi-asserted-by":"publisher","award":["REC.1402.166"],"award-info":[{"award-number":["REC.1402.166"]}],"id":[{"id":"10.13039\/501100006662","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Inflammation plays a critical role in tumor progression and drug resistance. Our previous research has repurposed carvedilol (CVL) to re\u2010sensitize paclitaxel (PTX)\u2010resistant gastric cancer AGS Cells (AGS\u2010Rpac) to PTX. This study aimed to evaluate the effects of combined CVL and PTX therapy on the modulation of inflammatory mediators and their associated signaling pathways. AGS\u2010Rpac cells were treated with specified concentrations of PTX and CVL. Levels of IL\u20101\u03b2 and TNF\u2010\u03b1 were measured. The expression levels of nuclear factor kappa B (NF\u2010\u03baB p65), NLR family pyrin domain containing 3 (NLRP3), as well as the \u03b22\u2010adrenergic receptor (\u03b22\u2010AR), \u03b2\u2010arrestin\u20102, and cyclic GMP\u2010AMP synthase (cGAS)\u2010stimulator of interferon genes (STING), were assessed by western blotting. CVL alone, and particularly PTX and CVL\u2009+\u2009PTX treatments, prompted a significant increase in NLRP3, NF\u2010\u03baB p65, IL\u20101\u03b2, and TNF\u2010\u03b1 inflammatory factors compared to the control. \u03b22\u2010AR expression was decreased in CVL\u2010treated cells compared to other groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). \u03b2\u2010Arrestin\u20102 and cGAS levels were increased in CVL monotherapy, whereas they were reduced in the PTX\u2010treated cells compared to the control. These protein levels were restored to near\u2010control levels with combination therapy. STING expression was upregulated in the control and CVL groups. The diminished levels of STING in PTX\u2010treated cells were slightly increased in combination therapy. The combination of PTX and CVL significantly increased levels of inflammatory factors. CVL appears to recruit \u03b2\u2010arrestin\u20102 to \u03b2\u2010adrenergic receptors, which, in turn, activate the cGAS\u2010STING pathway and induce the production of inflammatory factors.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70793","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T08:10:06Z","timestamp":1775808606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Carvedilol Upregulates Inflammatory Factors to Enhance Paclitaxel Sensitivity in Paclitaxel\u2010Resistant Gastric Cancer AGS Cells: Influences on \u03b2\u2010Arrestin\u20102\/cGAS\u2010STING Axis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4025-7997","authenticated-orcid":false,"given":"Haleh","family":"Salati Momeni","sequence":"first","affiliation":[{"name":"Digestive Disease Research Center Ardabil University of Medical Sciences Ardabil Iran"},{"name":"Research, Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine Ardabil University of Medical Sciences Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6124-5521","authenticated-orcid":false,"given":"Sarvin","family":"Tabibzadeh","sequence":"additional","affiliation":[{"name":"Research, Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine Ardabil University of Medical Sciences Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9013-4664","authenticated-orcid":false,"given":"Ali","family":"Niapour","sequence":"additional","affiliation":[{"name":"Digestive Disease Research Center Ardabil University of Medical Sciences Ardabil Iran"},{"name":"Research, Laboratory for Embryology and Stem Cells, Department of Anatomical Sciences, School of Medicine Ardabil University of Medical Sciences Ardabil Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i12.1187"},{"issue":"2","key":"e_1_2_11_3_1","first-page":"141","article-title":"Drug Resistance and Combating Drug Resistance in Cancer","volume":"2","author":"Wang X.","year":"2019","journal-title":"Cancer Drug Resistance"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122390"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2020.01.002"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-00886-5"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02160"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.11.059"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105933"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13167-019-00194-x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0300060519895347"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100050"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.03.003"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-021-01522-6"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217958"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202400725RR"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2019.104587"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.205"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-025-02966-0"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-022-02217-3"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0183662"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01108"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03041-4"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39858"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-09132-7"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804745105"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19849-9"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104866"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3558"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-05945-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-024-02326-4"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304328"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.5009\/gnl210359"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00524-z"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/imcb.12555"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2023.116448"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-67342-6"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001813-200404000-00001"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-2030-2"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.11.093"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-18324-3"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217038"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14133097"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/vco.12560"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70793","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70793","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70793","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T19:46:47Z","timestamp":1786564007000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70793"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/jbt.70793"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70793","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"assertion":[{"value":"2025-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70793"}}