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  • Title: Antisense treatment of IGF-IR enhances chemosensitivity in squamous cell carcinomas of the head and neck.
    Author: Liu S, Jin F, Dai W, Yu Y.
    Journal: Eur J Cancer; 2010 Jun; 46(9):1744-51. PubMed ID: 20451373.
    Abstract:
    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.
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