[Experimental study on human pancreatic carcinoma treated by cytosine deaminase gene therapy].
OBJECTIVE
To explore the possibility of Escherichia coli cytosine deaminase (CD) gene on human pancreatic carcinoma gene therapy.


METHODS
Recombinant adenoviruses containing a carcinoembryonic antigen (CEA) promoter were transiently introduced into SW1990, Capan-2 and Hela cells, separately. The expression of CD gene mRNA was examined by RT-PCR. CD protein level in the transduced cells was analyzed by Western blotting. The sensitivity of the cells to 5-fluorocytosine (5-FC) was determined by MTT assay.


RESULTS
A specific expression of cytosine deaminase gene by adenovirus-mediated transfer exhibited only in SW1990 cells (CEA-producing). Transduction of CD gene resulted in significant sensitivity of SW1990 cells to 5-FC. The anticancer effect was seen in vivo in SW1990 xenografts nude mice with in situ CD gene transduction.


CONCLUSIONS
The targeted expression of CD gene combined prodrug 5-FC may be a potential approach for gene therapy for human pancreatic carcinoma.
Zhang
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Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University of Medical Sciences, Guangzhou 510120, China.
Yuan
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D000230:Adenocarcinoma / Q000628:therapy*; D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002272:Carcinoembryonic Antigen / Q000032:analysis / Q000235:genetics; D003470:Culture Media; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000201:enzymology; D005437:Flucytosine / Q000494:pharmacology*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000473:pathology / Q000628:therapy; D009700:Nucleoside Deaminases / Q000096:biosynthesis / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011355:Prodrugs / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D002272:Carcinoembryonic Antigen; D003470:Culture Media; D011355:Prodrugs; D005437:Flucytosine; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase