{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:39:32Z","timestamp":1787791172902,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gemcitabine (GEM) is often used to treat pancreatic cancer. Many anti\u2010cancer drugs induce cancer cell death, but some cells survive after cell cycle arrest. Such a response to DNA damage is termed cellular senescence. Certain drugs, including the Bcl\u20102\u2010family inhibitor ABT\u2010263, kill senescent cells; this is termed senolysis. In this study, we examined the therapeutic benefits of ABT\u2010263 in GEM\u2010induced senescence of human pancreatic cancer cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Of four pancreatic cancer cell lines (PANC\u20101, AsPC\u20101, CFPAC\u20101, and PANC10.05), GEM induced senescent features in PANC\u20101 and AsPC\u20101 cells, including increases in the cell sizes and expression levels of mRNAs encoding interleukin (IL)\u20106\/IL\u20108 and induction of \u03b2\u2010galactosidase. Successive treatment with GEM and ABT\u2010263 triggered apoptosis in PANC\u20101 and AsPC\u20101 cells and suppressed colony formation significantly. Senolysis of GEM\u2010induced senescent pancreatic cancer cells by ABT\u2010263 was triggered by a Bcl\u2010xL inhibitor, but not by a Bcl\u20102 inhibitor, suggesting a central role for Bcl\u2010xL in senolysis. In a xenograft mouse model, combined treatment with GEM and ABT\u2010737 (an ABT\u2010263 analog exhibiting the same specificity) suppressed in vivo growth of AsPC\u20101 significantly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Together, our results indicate that sequential treatment with GEM and senolytic drugs effectively kill human pancreatic cancer cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cnr2.2075","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T15:28:55Z","timestamp":1714058935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Senolysis of gemcitabine\u2010induced senescent human pancreatic cancer cells"],"prefix":"10.1002","volume":"7","author":[{"given":"Mohammad Mahbubul","family":"Hoque","sequence":"first","affiliation":[{"name":"Department of Immunology Shimane University Faculty of Medicine  Izumo Shimane 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