Antisense MDM2 enhances the response of androgen insensitive human prostate cancer cells to androgen deprivation in vitro and in vivo

The Prostate
Zhaomei MuAlan Pollack

Abstract

Antisense MDM2 oligonucleotide (AS-MDM2) sensitizes androgen sensitive LNCaP cells to androgen deprivation (AD) in vitro and in vivo. In this study, we investigated the effects of AS-MDM2 combined with AD on androgen resistant LNCaP (LNCaP-Res) and moderately androgen resistant bcl-2 overexpressing LNCaP (LNCaP-BST) cells. The LNCaP-Res cell line was generated by culturing LNCaP cells in medium containing charcoal-stripped serum for more than 1 year. Apoptosis was quantified in vitro by Annexin V staining and caspase 3 + 7 activity. For the in vivo studies, orthotopic tumor growth was monitored by magnetic resonance imaging (MRI). AS-MDM2 and the mismatch control were given by i.p. injection at doses of 25 mg/kg per day, 5 days/week for 15 days. LNCaP-Res cells expressed high levels of androgen receptor (AR) and bcl-2, and displayed no growth inhibition to AD. AS-MDM2 caused significant reductions in MDM2 and AR expression, and increases in p53 and p21 expression in both cell lines. AS-MDM2 + AD 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-BST cells. AS-MDM2 + AD enhanced apoptotic cell death in vitro and tumor ...Continue Reading

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Citations

May 28, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Li-Yan KhorAlan Pollack
Jun 21, 2011·Cancer radiothérapie : journal de la Société française de radiothérapie oncologique·C ChargariE Deutsch
Dec 4, 2013·Journal of Experimental & Clinical Cancer Research : CR·Zhaomei MuMassimo Cristofanilli
Apr 25, 2016·Neoplasia : an International Journal for Oncology Research·Felix Y FengDaniel A Hamstra
Nov 26, 2010·Physics in Medicine and Biology·Lili ChenAlan Pollack
Jan 22, 2009·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·B MelladoP Gascón
Jan 11, 2019·Cancer Research·Premkumar Vummidi GiridharSusan Kasper
Apr 25, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity

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