Reference - Detail
|Author||Tomizawa M, Saisho H.|
|Title||Signaling pathway of insulin-like growth factor-II as a target of molecular therapy for hepatoblastoma.|
|Journal||World J Gastroenterol|
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.
|MeSH||Androstadienes / pharmacology Apoptosis / drug effects Cell Line, Tumor Cell Proliferation / drug effects Chromones / pharmacology Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Gene Expression Regulation, Neoplastic Hepatoblastoma / drug therapy* Hepatoblastoma / physiopathology* Humans Insulin-Like Growth Factor II / pharmacology Insulin-Like Growth Factor II / physiology* Liver Neoplasms / drug therapy* Liver Neoplasms / physiopathology* Morpholines / pharmacology Phosphoinositide-3 Kinase Inhibitors Receptor, IGF Type 1 / antagonists & inhibitors Receptor, IGF Type 1 / genetics Receptor, IGF Type 1 / metabolism Signal Transduction / physiology* Wortmannin|
|WOS Category||GASTROENTEROLOGY & HEPATOLOGY|
|Human and Animal Cells|