AIM: To address the possibility that insulin-like growth factor (IGF)-Ⅱ is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used. IGF-Ⅱ was added to the medium deprived of serum. Western blot analysis was performed to clarify the expression of IGF-I receptor (IGF-IR). Inhibitors of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF-Ⅱ. Cells were analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation.RESULTS: IGF-Ⅱ stimulated cells proliferated to 2.7 (269% ± 76%) (mean ± SD) (Huh-6) and 2.1 (211% ± 85%) times (HepG2). IGF-IR was expressed in Huh-6 and HepG2. PPP suppressed the cell number to 44% ± 11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin suppressed the cell number to 30% ± 5% (Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6) and 46% ± 1.1% (HepG2), respectively. PD98059 suppressed the cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis.CONCLUSION: IGF-Ⅱ was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy. AIM: To address the possibility that insulin-like growth factor (IGF) -II is a growth factor and its signaling pathway so as to develop a molecular therapy for hepatoblastoma. METHODS: Huh-6 and HepG2, human hepatoblastoma cell lines, were used . Inhibition of IGF-IR (piclopodophyllin, PPP), phosphatidyl-inositol (PI) Inhibitors of IGF- 3-kinase (LY294002 and Wortmannin), or mitogen-activated protein (MAP) kinase (PD98059) were added to unveil the signaling pathway of IGF- II. Cells were previously analyzed morphologically with hematoxylin-eosin staining to reveal the mechanism of suppression of cell proliferation.RESULTS: IGF-I was expressed in Huh-6 and 2.1 (211% ± 85%) times (HepG2). IGF-IR was expressed in Huh -6 and HepG2. PPP suppressed the cell number to 44% ± 11% (Huh-6) and 39% ± 5% (HepG2). LY294002 and Wortmannin s uppressed the cell number to 30% ± 5% (Huh-6), 44% ± 0.4% (HepG2), 49% ± 1.0% (Huh-6) and 46% ± 1.1% (HepG2) cell number to 33% ± 11% for HepG2 but not for Huh-6. When cell proliferation was prohibited, many Huh-6 and HepG2 cells were dead with pyknotic or fragmented nuclei, suggesting apoptosis. CONCLUSION: IGF-II was shown to be a growth factor of hepatoblastoma via IGF-I receptor and PI3 kinase which were good candidates for target of molecular therapy.