Overexpression of pyrimidine nucleoside phosphorylase enhances the sensitivity to 5'-deoxy-5-fluorouridine in tumour cells in vitro and in vivo

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
T NagataH Yamaue

Abstract

5-Fluorouracil (5-FU) and 5'-deoxy-5-fluorouridine (5'-DFUR), a prodrug of 5-FU, are representative of the chemotherapeutic agents for colorectal adenocarcinomas. Pyrimidine nucleoside phosphorylase (PyNPase) catalyses the conversion of 5'-DFUR to 5-FU, the activated form. Murine adenocarcinoma CT26 cells were transfected with human PyNPase cDNA. The engineered transfectants producing PyNPase augmented the response to 5'-DFUR in vitro and in vivo. Animals were administered by means of intraperitoneal (i.p.) injection, and not orally, in order to obtain a better efficiency of absorption. The tumours of the transfected cells nearly all disappeared, even following treatment with quite a small amount of the anticancer agent. The animals injected with the tranfected cells were protected against subsequent challenge with the parental tumour cell line. These findings demonstrate that PyNPase gene transfection increases the sensitivity to 5'-DFUR, and thereby decreases the toxicity of the agent.

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Citations

Dec 23, 2008·Applied Biochemistry and Biotechnology·Chongtao GeLing Ou
Feb 20, 2007·Molecular Aspects of Medicine·Daniel PortsmouthMatthias Renner
Oct 4, 2015·The Biochemical Journal·Elsie M WilliamsDavid F Ackerley
Jun 25, 2016·World Journal of Gastroenterology : WJG·Ting LiuYong-Heng Chen
Jan 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Guiying ZhangXiuwu Zhang

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