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Enhanced Cytotoxicity of 5-FU by bFGF through Up-Regulation of Uridine Phosphorylase 1

  • Im, Young-Sam (Department of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Shin, Hea Kyeong (Department of Plastic Surgery, College of Medicine, Dongguk University) ;
  • Kim, Hye-Ryun (Department of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Jeong, So-Hee (Department of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Kim, Seung-Ryul (Department of Biochemistry, College of Medicine, Chungbuk National University) ;
  • Kim, Yong-Min (Department of Orthopaedic Surgery, College of Medicine, Chungbuk National University) ;
  • Lee, Do Hyung (Gyeonggi Regional Research Center, Hankyoung National University) ;
  • Jeon, Seong-Ho (College of Pharmacy, Kangwon National University) ;
  • Lee, Hyeon-Woo (Department of Pharmacology, School of Dentistry, Kyung Hee University) ;
  • Choi, Joong-Kook (Department of Biochemistry, College of Medicine, Chungbuk National University)
  • Received : 2009.06.11
  • Accepted : 2009.07.10
  • Published : 2009.08.31

Abstract

Anti cancer agent 5-FU (Fluoro Uracil) is a prodrug that can be metabolized and then activated to interfere with RNA and DNA homeostasis. However, the majority of administered 5-FU is known to be catabolized in vivo in the liver where Dihydropyrimidine dehydrogenase (DPD) is abundantly expressed to degrade 5-FU. The biological factors that correlate with the response to 5-FU-based chemotherapy have been proposed to include uridine phosphorylase (UPP), thymidine phosphorylase (TPP), p53 and microsatellite instability. Among these, the expression of UPP is known to be controlled by cytokines such as $TNF-{\alpha}$, IL1 and $IFN-{\gamma}$. Our preliminary study using a DNA microarray technique showed that basic fibroblast growth factor (bFGF) markedly induced the expression of UPP1 at the transcription level. In the present study, we investigated whether bFGF could modulate the expression of UPP1 in osteo-lineage cells and examined the sensitivity of these cells to 5-FU mediated apoptosis.

Keywords

5-DFUR (= 5-dFURd);5-FU;apoptosis;ATDC5 chondroprogenitor cells;bFGF;C2C12 pre-myoblasts;$NF{\kappa}B$;uridine phosphorylase

Acknowledgement

Supported by : Korea Science and Engineering Foundation (KOSEF), Chungbuk National University

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