{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:36:34Z","timestamp":1772084194664,"version":"3.50.1"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,1,14]],"date-time":"2008-01-14T00:00:00Z","timestamp":1200268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Antisense MDM2 oligonucleotide (AS\u2010MDM2) sensitizes androgen sensitive LNCaP cells to androgen deprivation (AD) in vitro and in vivo. In this study, we investigated the effects of AS\u2010MDM2 combined with AD on androgen resistant LNCaP (LNCaP\u2010Res) and moderately androgen resistant bcl\u20102 overexpressing LNCaP (LNCaP\u2010BST) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The LNCaP\u2010Res cell line was generated by culturing LNCaP cells in medium containing charcoal\u2010stripped serum for more than 1 year. Apoptosis was quantified in vitro by Annexin V staining and caspase 3\u2009+\u20097 activity. For the in vivo studies, orthotopic tumor growth was monitored by magnetic resonance imaging (MRI). AS\u2010MDM2 and the mismatch control were given by i.p. injection at doses of 25 mg\/kg per day, 5 days\/week for 15 days.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>LNCaP\u2010Res cells expressed high levels of androgen receptor (AR) and bcl\u20102, and displayed no growth inhibition to AD. AS\u2010MDM2 caused significant reductions in MDM2 and AR expression, and increases in p53 and p21 expression in both cell lines. AS\u2010MDM2\u2009+\u2009AD resulted in the highest levels of apoptosis in vitro and tumor growth inhibition in vivo in both cell lines; although, these effects were less pronounced in LNCaP\u2010BST cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>AS\u2010MDM2\u2009+\u2009AD enhanced apoptotic cell death in vitro and tumor growth inhibition in vivo in androgen resistant cell lines. The action of AS\u2010MDM2\u2009+\u2009AD was influenced somewhat by bcl\u20102 expression as an isolated change (LNCaP\u2010BST cells), but not when accompanied by other molecular changes associated with androgen insensitivity (LNCaP\u2010Res cells). MDM2 knockdown has promise for the treatment of men with early hormone refractory disease. Prostate 68: 599\u2013609, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.20731","type":"journal-article","created":{"date-parts":[[2008,1,14]],"date-time":"2008-01-14T17:52:13Z","timestamp":1200333133000},"page":"599-609","source":"Crossref","is-referenced-by-count":21,"title":["Antisense MDM2 enhances the response of androgen insensitive human prostate cancer cells to androgen deprivation in vitro and in 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