Growth inhibitory effects of pegylated IFN-alpha2b and 5-fluorouracil in combination on renal cell carcinoma cell lines in vitro and in vivo.
We investigated the effects of pegylated IFN-alpha2b (PEG-IFN-alpha2b) alone and PEG-IFN-alpha2b plus 5-fluorouracil (5-FU) in vitro on the proliferation of renal cell carcinoma (RCC) cell lines. After the transplantation of RCC cells into nude mice, we administered IFN (PEG-IFN-alpha2b or IFN-alpha2b) alone, 5-FU alone, or IFN (PEG-IFN-alpha2b or IFN-alpha2b) plus 5-FU; and investigated tumor volume, tumor weight, the numbers of apoptotic cells and artery-like blood vessels, relative mRNA expression levels of enzymes which relate to 5-FU metabolism, angiogenesis factor, and type I interferon receptor. RCC cells in vitro were generally and relatively resistant to the anti-proliferative effects of PEG-IFN-alpha2b, but the addition of 5-FU augmented IFN-induced anti-proliferative effects with the induction of apoptosis. PEG-IFN-alpha2b in vivo presented stronger anti-tumor effects than IFN-alpha2b, and its combination with 5-FU augmented the effects. The significant anti-tumor effect of the combination treatment was the increase in apoptotic cell number, but there were no significant differences in the suppression of angiogenesis, expression of IFN receptor, and the actions of metabolic enzymes of 5-FU. In conclusion, PEG-IFN-alpha2b presents stronger anti-tumor effects than non-pegylated IFN, and the effects are augmented in the combination with 5-FU. Our findings suggest the clinical usefulness of PEG-IFN-alpha2b in the treatment of RCC.
Moriya
Fukuko
F
Department of Pathology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan. moriya_fukuko@kurume-u.ac.jp
Ogasawara
Sachiko
S
Basaki
Yuji
Y
Akiba
Jun
J
Kojiro
Sakiko
S
Fukahori
Suguru
S
Ishizaki
Hironori
H
Nishida
Naoyo
N
Matsuoka
Kei
K
Kojiro
Masamichi
M
Kuwano
Michihiko
M
Yano
Hirohisa
H
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D017690:Cell Transplantation; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins
D000964:Antimetabolites, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D005472:Fluorouracil