Therapeutic effect of AdCMVCD／5—FC system and metabolism of 5—FC in the treatment of human tongue squamous cell carcinoma

Objective To investigate the therapeutic effect and metabolism of 5-fluorocytosin(5-FC)in human tondue squamous carcinoma cells after treatment with adenovirus-mediated cytosine deaminase(AdCMVCD)/5-FC system.Methods Human tongue squamous carcinoma cells(Tca8113 cell line)and its xenografts in BALB/c nude mice were treated with AdCMVCD/5-FC system.The killing effect in vitro and bystander effect were detected by microculture tetrazolium(MTT)assay.Tumor inhibition effect and histopathological changes were observed in vivo.High-performance liquid chromatography(HPLC) was performed to determine the metabolism of 5-FC in vitro and in vivo.Results AdCMVCD/5-FC system had strong killing effect and bystander effect on Tca8113 cells.Both condition media and cell extracts showed two peaks identified as 5-FC and t-fluorouracil(5-FU0 by HPLC and a time-dependent generation of 5-FU and concomitant time-dependent decreases of 5-FC.Compared to the control groups,mice treated with AdCMVCD/5-FC system demonstrated significant tumor regression(P