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.

Keywords: :

• Chemoresistance
• Doxorubicin
• IGF1R-targeted therapy
• Osteosarcoma

ACKNOWLEDGMENTS

We would like to thank Professor David Thomas from Peter MacCallum Cancer Centre, University of Melbourne, for providing some osteosarcoma cell lines and also thank Dr. Jonathan Kuang for performing western blotting analysis. This project was kindly supported by a project grant from Australian Orthopaedic Association.