Low Dose Histone Deacetylase Inhibitor, Depsipeptide FR901228, Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell LinesReport as inadecuate




Low Dose Histone Deacetylase Inhibitor, Depsipeptide FR901228, Promotes Adenoviral Transduction in Human Rhabdomyosarcoma Cell Lines - Download this document for free, or read online. Document in PDF available to download.

Sarcoma - Volume 8 2004, Issue 1, Pages 25-30



Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda 20892-1928, MD, USA

Department 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 hasbeen limited by the low to absent levels of coxackie and adenovirus receptor CAR. This study investigates the potential useof low doses of a histone deacetylase inhibitor, depsipeptide FR901228, currently in Phase II human trials, to enhanceadenoviral uptake in six rhabdomyosarcoma cell lines.

Methods. Differences in adenoviral uptake in the presence and absence of depsipeptide FR901228 were assessed using anadenoviral construct tagged with green fluorescent protein. Changes in CAR and αv integrin expression RMS in response topretreatment 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 increasedviral uptake as assessed by green fluorescent protein expression. RT-PCR analysis for CAR showed that in four of these fivecell 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 inresponse 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 RMScells. The mechanism of increased viral uptake appears to mediate via upregulation of CAR.





Author: Fariba Navid, Blaine T. Mischen, and Lee J. Helman

Source: https://www.hindawi.com/



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