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 digest ive tract cancers, and chemotherapy is the treatment of choice for many pat ients. In this study, we experimentally introduced an Escherichia coli-deri ved uracil phosphoribosyltransferase (UPRT) gene to cultured esophageal can cer cell lines to potentiate the antitumor effects of a representative anti cancer 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 i n 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 sensi tivity by UPRT gene transduction in vivo. Therefore, we potentiated the eff ects of commercially available anticancer drugs by gene transduction. Our m ethod may prove useful as a new form of cancer gene therapy in the future.