Surgical & Orthopaedics Research, University of New South Wales, Sydney, Australia.
Cancer Invest. 2011 Oct;29(8):521-32. doi: 10.3109/07357907.2011.606252. Epub 2011 Aug 15.
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.
I 型胰岛素样生长因子受体（IGF1R）及其信号通路在骨肉瘤的发生、肿瘤进展和化疗耐药中起着重要作用。本研究的目的是在一组六种骨肉瘤细胞系和一个自行建立的多柔比星耐药细胞系中，研究 IGF1R 抑制物 tyrphostin AG1024 在存在或不存在多柔比星的情况下的作用及其机制。我们首次表明，与多柔比星联合靶向 IGF1R 可获得相加的抗骨肉瘤生长效果，同时伴有细胞凋亡增加、细胞毒性增加和双重细胞周期阻滞。总之，IGF1R 抑制可增强某些骨肉瘤细胞系的多柔比星化疗效果。
