title: IGF1R-targeted therapy and its enhancement of doxorubicin chemosensitivity in human osteosarcoma cell lines.
abstract: Type-I insulin-like growth factor receptor (IGF1R) and its signaling play an important role in osteosarcomagenesis, tumor progression, and chemoresistance. The purpose of this study was to investigate both the effect and mechanisms of IGF1R inhibition by tyrphostin AG1024 in the presence or absence of doxorubicin in a panel of six osteosarcoma cell lines and a self-established doxorubicin-resistant cell line. We are the first to indicate that targeting IGF1R together with doxorubicin achieved additive anti-osteosarcoma growth effect, accompanied with increased apoptosis, cytotoxicity, and dual cell cycle arrests. In conclusion, IGF1R inhibition can enhance doxorubicin chemotherapy in some osteosarcoma cell lines.
authors.affiliation: Surgical & Orthopaedics Research, University of New South Wales, Sydney, Australia.
authors.forename: Frederick
authors.initials: F
authors.lastname: Luk
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: William R
authors.initials: WR
authors.lastname: Walsh
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Yang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000037:antagonists & inhibitors*; D020032:Tyrphostins / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D020032:Tyrphostins; C447031:tyrphostin AG 1024; D004317:Doxorubicin; D017526:Receptor, IGF Type 1