[Anti-tumor effects of various interferons-alpha +5-fluorouracil via downregulation of dihydropyrimidine dehydrogenase in hepatoma cells].
OBJECTIVE
Systemic chemotherapy has not seen widespread use in the treatment for hepatocellular carcinoma (HCC). Recently, it was reported that combination treatment of 5-fluorouracil (5-FU) and interferon (IFN)-alpha was effective for non-resectable HCC. The effect of 5-FU treatment is influenced by the activities of pyrimidine catabolic enzymes. The aim of this study was to investigate which IFN-alphais most effective in combination therapy via downregulation of dihydropyrimidine dehydrogenase (DPD).


METHODS
Cell proliferation assay in human hepatoma cells (HepG 2) was performed using 5-FU and/or various IFNs-alpha (C-IFN, Intron A, OIF). At the same time,DPD mRNA levels were quantified by real-time polymerase chain reaction.


RESULTS
5-FU alone but not all the IFNs showed anti-cancer effects, and the combination of each IFN +5-FU had a greater anti-cancer effect than 5-FU alone. C-IFN +5-FU most effectively prevented cancer cell proliferation (p < 0.05). Also, the combination of C-IFN +5-FU most downregulated DPD mRNA expression.


CONCLUSIONS
The combination of each IFN-alpha +5-FU showed anti-cancer effects for HCC via downregulation of DPD. C-IFN may be most effective in the combination therapy of IFN-alpha +5-FU for HCC.
Fan
Xiao Yan
XY
Dept. of Surgery, Oita University Faculty of Medicine.
Uchida
Hiroki
H
Iwaki
Kentaro
K
Kai
Seiichiro
S
Shibata
Kohei
K
Ohta
Masayuki
M
Kitano
Seigo
S
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division; D045744:Cell Line, Tumor; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism*; D015536:Down-Regulation; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000473:pathology*
D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil