Improved sensitivity of gastric carcinoma cells to fluorouracil-related drugs by transfection of thymidine phosphorylase gene / 中华病理学杂志
Chinese Journal of Pathology
;
(12): 330-333, 2011.
Article
in Chinese
| WPRIM
| ID: wpr-261789
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the relationship between the expression of thymidine phosphorylase (TP) and the sensitivity of gastric carcinoma to 5-fluorouracil (5-FU) and its prodrugs.</p><p><b>METHODS</b>Gastric carcinoma cell line AGS was transfected with recombinant plasmid pEGFP-N1-TP or control plasmid pEGFP-N1 by lipofectamin 2000. The expression of green fluorescence labeled protein was observed under fluorescence microscope. Positive clones AGS-p and AGS-pTP were selected by G418 treatment. Expression of TP protein and mRNA was detected by immunocytochemistry and RT-PCR, respectively. Drug sensitivity to 5-FU and its prodrugs was assessed by MTT assay.</p><p><b>RESULTS</b>Cell clones with the expression of green fluorescent protein (AGS-p) and a clone with TP and green fluorescent fusion protein (AGS-pTP) were established. Immunostaining of TP protein was strongly positive in AGS-pTP and negative in AGS-p and AGS. The expression of TP mRNA was significantly higher in AGS-pTP (0.8090 ± 0.0450) than that in AGS (0.0490 ± 0.0046) and AGS-p (0.0610 ± 0.0069; P < 0.01). The sensitivity to doxifluridine and capecitabine in AGS-pTP was significantly increased, as compared with that in AGS-p. IC50 values of AGS-pTP to doxifluridine and capecitabine were estimated 1.7 folds and 2.2 folds as much as that of AGS-p, respectively. The sensitivity to 5-FU was not different between AGS-pTP and AGS-p.</p><p><b>CONCLUSIONS</b>Enhancement of TP expression improves the sensitivity of gastric carcinoma cells to doxifluridine and capecitabine. But it does not affect the sensitivity to 5-FU.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Plasmids
/
Stomach Neoplasms
/
Thymidine Phosphorylase
/
Recombinant Proteins
/
RNA, Messenger
/
Transfection
/
Sensitivity and Specificity
/
Floxuridine
Type of study:
Diagnostic study
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Pathology
Year:
2011
Type:
Article
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