Enhanced cytotoxicity of 5-FU by bFGF through up-regulation of uridine phosphorylase 1.
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.
Im
Young-Sam
YS
Department of Biochemistry, College of Medicine, Chungbuk National University, Cheongju, 361-763, Korea.
Shin
Hea Kyeong
HK
Kim
Hye-Ryun
HR
Jeong
So-Hee
SH
Kim
Seung-Ryul
SR
Kim
Yong-Min
YM
Lee
Do Hyung
DH
Jeon
Seong-Ho
SH
Lee
Hyeon-Woo
HW
Choi
Joong-Kook
JK
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*; D014543:Uridine Phosphorylase / Q000235:genetics*
D000964:Antimetabolites, Antineoplastic; D016222:Fibroblast Growth Factor 2; D014543:Uridine Phosphorylase; D005472:Fluorouracil