{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:59:47Z","timestamp":1785437987820,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Lung cancer is a deadly disease that affects the tissues in the lungs. It is the leading cause of cancer\u2010related deaths worldwide, accounting for approximately 1.8 million deaths each year. The inhibitor of kappa B kinase alpha (IKK\u03b1) is a key component of NF\u2010\u03baB signaling with stimulatory functions in inflammation, proliferation, and metastasis, and also contributes to the development of treatment resistance. Hence, we examine the effects of IKK\u03b1 silencing on the proliferation, sensitization of cells to doxorubicin, apoptosis and metastasis of A549 human lung cancer cell line and its downstream signal transduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>This study focused on investigating the effects of IKK\u03b1 in the doxorubicin (DOX) mediated apoptosis with further detailed mechanisms in lung cancer. siRNA was used to silence IKK\u03b1. Cell viability was measured using an MTT assay. Western blot and qRT\u2010PCR were used for the measurement of target proteins and mRNA expression levels. ELISA cell death assay was used to measure apoptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>Simultaneous silencing of IKK\u03b1 and treatment with DOX led to a dramatic elevation in the cytotoxic effects of DOX in A549 cells. In addition, siRNA against IKK\u03b1 increased apoptosis and decreased metastasis in resistant cells. Moreover, si\u2010IKK\u03b1 downregulated the expression levels of CDK1\/PI3K\/AKT IKK\u03b1 silencing led to the reversal of DOX resistance in A549 cells. IKK\u03b1 silencing and DOX exposure elevated the DOX mediated cellular cytotoxicity by targeting the CDK1\/PI3K\/AKT axis, and apoptosis induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>These findings suggest that PI3K\u2010IKK\u03b1\u2010CDK1 may be a promising therapeutic strategy for human lung cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbt.70505","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:14:31Z","timestamp":1760598871000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting PI3K\u2010IKK\u03b1\u2010CDK1 Signaling Pathway to Prevent Lung Cancer Progression and Resistance"],"prefix":"10.1002","volume":"39","author":[{"given":"Wei","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Baoji Traditional Chinese Medicine Hospital Baoji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahman","family":"Yousefi","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Department Tehran University of Medical Sciences Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Baoji Traditional Chinese Medicine Hospital Baoji 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