MASAMICHI Kojiro Kurume University, School of Medicine, Professor, 医学部, 教授 (90080580)
OGASAWARA Sachiko Kurume University, School of Medicine, Fellow, 医学部, 助手 (40258405)
MOMOSAKI Seiya Kurume University, School of Medicine, Instructor, 医学部, 講師 (40279138)
|Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
[Purpose] In this study, we examined that the effects of IFN-α subtypes on the growth of human liver cancer cell lines in vitro ; growth inhibitory effects of IFN-α and 5-Fu in vitro ; mechanisms of apoptosis induction by IFN-α; and the effects of IFN-α alone or IFN-α plus 5-Fu on the growth of human liver cancer cell lines transplanted In nude mice.
[Results] 1. When we examined the effects of five kinds of recombinant IFN-α subtypes (α1, α2, α5, α8, α10; concentrations: 0-1024 IU/mL; 24-96 hours) on the growth of 13 human liver cancer cell lines, the strongest anti-proliferative effects was noted In IFN-α5 subtype, and followed by α8, α10, α2, α1. 2. No synergistic growth Inhibitory effects could be recognized when IFN-α and 5-Fu were simultaneously added t o the culture of liver cancer cells. 3. Natural human IFN-α induced activation of caspase-3, -7, -8, and -9, and proteolysis of PARP in IFN-α-induced apoptosis-sensitive cell lines at various degrees. In addition, release of cytochrome C and Smac/Diablo from mitochondria into cytoplasm was identified in IFN-α-treated cells time-dependently. These findings suggest mitochondria apoptosis induction pathway is involved in the IFN-α-induced apoptosis. 4. Subcutaneous IFN-αCon1 injection (0.01, 0.1, 1μg/mouse/day; 0.01 μg/mouse = clinical dosesage) for consecutive 14 days dose-and time-dependently suppressed the HCC tumor growth in nude mice. Finally, the tumor volumes of mice received 0.01, 0.1, and 1 μg/mouse of IFN-αCon1 decreased to about 60%, 25%,and 0-10%, respectively, of control tumor volumes. The number of apoptotic cells significantly Increased and the number of blood vessels significantly decreased with the increase of IFN-αCon1 dose. 5. Synergistic effect of IFN-α plus 5-Fu was identified In nude mouse tumors. [Conclusions] These data Indicate the potential clinical application of certain types of IFN-α in the prevention and treatment of HCC.