Adenovirus-mediated transduction of Escherichia coli uracil phosphoribosyltransferase gene increases the sensitivity of esophageal cancer cells to 5-fluorouracil.
Esophageal cancer is associated with the poorest prognosis among the digestive tract cancers, and chemotherapy is the treatment of choice for many patients. In this study, we experimentally introduced an Escherichia coli-derived uracil phosphoribosyltransferase (UPRT) gene to cultured esophageal cancer cell lines to potentiate the antitumor effects of a representative anticancer drug, 5-fluorouacil (5-FU). UPRT is a pyrimidine salvage enzyme that catalyzes the synthesis of uridine monophosphate from uracil and PRPP. The UPRT gene was transduced into five cultured esophageal cancer cell lines, TE1, TE2, TE3, NUEC1, and T.T, using an adenovirus vector. It was confirmed that the sensitivities of all cultured cell lines to 5-FU were increased in vitro. Subsequently, the T.T line was subcutaneously inoculated into nude mice to induce tumors, after which 5-FU was administered intraperitoneally. When a UPRT gene-recombinant adenovirus vector was directly injected into the tumors, tumor proliferation was markedly inhibited compared with that in the group treated with 5-FU alone, suggesting potentiation of 5-FU sensitivity by UPRT gene transduction in vivo. Therefore, we potentiated the effects of commercially available anticancer drugs by gene transduction. Our method may prove useful as a new form of cancer gene therapy in the future.
Nakamura
H
H
Department of Surgery II, Nagoya University School of Medicine, Aichi, Japan.
Sekiguchi
H
H
Akiyama
S
S
Hamada
H
H
Fujiwara
M
M
Kasai
Y
Y
Ito
K
K
Nakao
A
A
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D004357:Drug Synergism; D004926:Escherichia coli / Q000201:enzymology*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D010430:Pentosyltransferases / Q000235:genetics*; D012680:Sensitivity and Specificity; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D010430:Pentosyltransferases; C023269:uracil phosphoribosyltransferase; D005472:Fluorouracil