摘要

To evaluate whether targeting IGF-IR therapeutic can increased chemosensitivity of squamous cell carcinomas of the head and neck (SCCHN) to doxorubicin and cisplatin, Insulin-like growth factor type I receptor (IGF-IR) expression was down-regulated by treatment with AS[S]ODN. Different doses of AS[S]ODN with doxorubicin or cisplatin were tested in TU159 and 183A SCCHN cell lines. Compared to phosphorothioate sense oligonucleotides (SS[S]ODN), AS[S]ODN treatment inhibited cancer cell proliferation and attenuated activation of IGF-IR. AS[S]ODN treatment was shown to enhance the sensitivity of SCCHN cell lines to doxorubicin and cisplatin. This observation correlated closely with the induction of apoptosis as measured by Annexin-V/PI and caspase activation assays. The in vivo results showed that treatment with AS[S]ODN/doxorubicin in combination also resulted in a significant suppression in TU159 xenografts. In conclusion, this study provides evidence for the efficacy of IGF-IR down-regulation combined with chemotherapy and raises the possibility that SCCHN treatment may be improved by pharmaceutical strategies directed towards the IGF-IR.