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Sarcoma
Volume 8, Issue 1, Pages 25-30
http://dx.doi.org/10.1080/13577140410001679220

Low Dose Histone Deacetylase Inhibitor, Depsipeptide (FR901228), Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell Lines

1Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892-1928, MD, USA
2Department of Hematology/Oncology, St. Jude Children's Research Hospital, 332 N. Lauderdale Street, Memphis 38105-2974, TN, USA

Copyright © 2004 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. Transduction of rhabdomyosarcoma (RMS) cells with adenoviral vectors for in vivo and in vitro applications has been limited by the low to absent levels of coxackie and adenovirus receptor (CAR). This study investigates the potential use of low doses of a histone deacetylase inhibitor, depsipeptide (FR901228), currently in Phase II human trials, to enhance adenoviral uptake in six rhabdomyosarcoma cell lines.

Methods. Differences in adenoviral uptake in the presence and absence of depsipeptide (FR901228) were assessed using an adenoviral construct tagged with green fluorescent protein. Changes in CAR and αv integrin expression RMS in response to pretreatment with depsipeptide (FR901128) was determined using RT-PCR.

Results. Pretreatment of five of six RMS cell lines with 0.5 ng/ml of depsipeptide (FR901228) for 72 h resulted in increased viral uptake as assessed by green fluorescent protein expression. RT-PCR analysis for CAR showed that in four of these five cell lines, CAR expression was increased 2.8–8.1-fold in cells treated with depsipeptide (FR901228) as compared to control. αv integrin expression was substantially increased in the one cell line, RH5, which showed increased GFP expression in response to depsipeptide (FR901228) pretreatment but a minimal increase in CAR expression.

Conclusions. Depsipeptide (FR901228) can be used as a vehicle to enhance adenoviral transduction in a majority of RMS cells. The mechanism of increased viral uptake appears to mediate via upregulation of CAR.