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.
