To investigate the therapeutic effect and metabolism of 5 fluorocytosine (5 FC ) in human tongue squamous carcinoma cells after treatment with adenovirus medi ated cytosine deaminase (AdCMVCD)/5 FC system Method...To investigate the therapeutic effect and metabolism of 5 fluorocytosine (5 FC ) in human tongue squamous carcinoma cells after treatment with adenovirus medi ated 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 m etabolism of 5 FC in vitro and in vivo Results AdCMVCD/5 FC system had strong killing effect and bystander effect on Tca8113 c ells Both condition media and cell extracts showed two peaks identified as 5 FC and 5 fluorouracil (5 FU) by HPLC and a time dependent generation of 5 FU and concomitant time dependent decreases of 5 FC Compared to the control gr oups, mice treated with AdCMVCD/5 FC system demonstrated significant tumor regr ession ( P <0 001); the tumor doubling time prolonged and inhibition rate was 92 62% There were substantial tumor necrotic areas and infiltrative lymphocy tes around necrotic areas in the AdCMVCD/5 FC treated group under light microsc ope There was a significantly low concentration of 5 FC and high concentratio n of 5 FU in tumor tissue, but only 5 FC was found in blood Conclusion AdCMVCD/5 FC suicide gene system had significant in vitro and in vivo anti tum or effect on human tongue squamous cell carcinoma due to convert 5 FC into 5 F U展开更多
基金Thisworkwassupportedbyagrantfrom"The 2 1 1project"ofSunYatSenUniversityofMedicalSciences (No 990 74)
文摘To investigate the therapeutic effect and metabolism of 5 fluorocytosine (5 FC ) in human tongue squamous carcinoma cells after treatment with adenovirus medi ated 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 m etabolism of 5 FC in vitro and in vivo Results AdCMVCD/5 FC system had strong killing effect and bystander effect on Tca8113 c ells Both condition media and cell extracts showed two peaks identified as 5 FC and 5 fluorouracil (5 FU) by HPLC and a time dependent generation of 5 FU and concomitant time dependent decreases of 5 FC Compared to the control gr oups, mice treated with AdCMVCD/5 FC system demonstrated significant tumor regr ession ( P <0 001); the tumor doubling time prolonged and inhibition rate was 92 62% There were substantial tumor necrotic areas and infiltrative lymphocy tes around necrotic areas in the AdCMVCD/5 FC treated group under light microsc ope There was a significantly low concentration of 5 FC and high concentratio n of 5 FU in tumor tissue, but only 5 FC was found in blood Conclusion AdCMVCD/5 FC suicide gene system had significant in vitro and in vivo anti tum or effect on human tongue squamous cell carcinoma due to convert 5 FC into 5 F U
