[Killing effect of adenovirus mediated fusion gene cytosine and deaminase uracil phosphoribosyl transferase directed by glutathione S-transferase P1 promoter on cisplatin-resistant ovarian cancer cells in vitro].
OBJECTIVE
To construct an adenoviral vector in which the fusion gene cytosine and uracil phosphoribosyl (UPP) transferase was directed by glutathione S-transferase P1 (GSTP1) promoter, and to investigate specific killing effect of the suicide gene system on cisplatin-resistant ovarian cancer cells.


METHODS
Recombinant adenovirus was generated through homologous recombination in bacteria. A2780 and A2780/DDP cells were infected with Ad and then received flucytosine (5-FC) administration. The relative survival of these cells was tested. And a bystander effect was observed by mixing gene-transferred and gene-untransferred A2780/DDP cells with 5-FC.


RESULTS
In vitro, when MOI was 100 and 5-FC was 250 micro g/ml, relative survival rate of A2780/DDP cells was only (3.6 +/- 1.0)%; that of A2780 cells was (76.5 +/- 2.8)%. Significant bystander effect was caused by CD-UPP gene and 20% gene-transferred A2780/DDP cells induced 80.3% of total cells to death.


CONCLUSIONS
Recombinant adenovirus carrying CD-UPP gene driven by GSTP1 promoter has a specific killing effect on cisplatin-resistant ovarian cancer cells.
Cai
Li-Qiong
LQ
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Li
Min
M
Lu
Shi
S
Wang
Hong-Bo
HB
Wang
Ze-Hua
ZH
D000260:Adenoviruses, Human / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D043525:Cytosine Deaminase / Q000235:genetics*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005437:Flucytosine / Q000627:therapeutic use; D015316:Genetic Therapy; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000473:pathology*; D010430:Pentosyltransferases / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; D005437:Flucytosine; D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D043525:Cytosine Deaminase; D002945:Cisplatin