Therapeutic effect of AdCMVCD/5-FC system and metabolism of 5-FC in the treatment of human tongue squamous cell carcinoma / 中华医学杂志(英文版)
Chinese Medical Journal
;
(24): 248-252, 2003.
Article
in English
| WPRIM
| ID: wpr-356823
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the therapeutic effect and metabolism of 5-fluorocytosine (5-FC) in human tongue squamous carcinoma cells after treatment with adenovirus-mediated cytosine deaminase (AdCMVCD)/5-FC system.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 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 groups, mice treated with AdCMVCD/5-FC system demonstrated significant tumor regression (P < 0.001); the tumor doubling time prolonged and inhibition rate was 92.62%. There were substantial tumor necrotic areas and infiltrative lymphocytes around necrotic areas in the AdCMVCD/5-FC treated group under light microscope. There was a significantly low concentration of 5-FC and high concentration of 5-FU in tumor tissue, but only 5-FC was found in blood.</p><p><b>CONCLUSION</b>AdCMVCD/5-FC suicide gene system had significant in vitro and in vivo anti-tumor effect on human tongue squamous cell carcinoma due to convert 5-FC into 5-FU.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Therapeutics
/
Transplantation, Heterologous
/
Tongue Neoplasms
/
Tumor Cells, Cultured
/
Carcinoma, Squamous Cell
/
Genetic Therapy
/
Adenoviridae
/
Cytosine Deaminase
/
Therapeutic Uses
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Chinese Medical Journal
Year:
2003
Type:
Article
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