Antisense treatment of IGF-IR enhances chemosensitivity in squamous cell carcinomas of the head and neck.
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.
Liu
Shiguo
S
Tongji Medical College, Huazhong University of Science and Technology, China.
Jin
Fengling
F
Dai
Wuxing
W
Yu
Yongfeng
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D054735:Phosphorothioate Oligonucleotides / Q000494:pharmacology*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D042461:Vascular Endothelial Growth Factor A; D004317:Doxorubicin; D017526:Receptor, IGF Type 1; D020169:Caspases; D002945:Cisplatin