- 作者：Oliver Riesterer M.D.* ; Qiuan Yang M.D.* ; Uma Raju Ph.D.* ; Mylin Torres M.D.* ; David Molkentine B.S.* ; Nalini Patel B.Sc.* ; David Valdecanas B.S.* ; Luka Milas M.D. ; Ph.D.* ; K. Kian Ang M.D. ; Ph.D.† ; ; kianang@mdanderson.org
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2011
- 出版时间：15 March 2011
- 年：2011
- 卷：79
- 期：4
- 页码：1179-1187
- 全文大小：749 K
Purpose
The IGF1/IGF-1R signaling pathway has emerged as a potential determinant of radiation resistance in human cancer cell lines. Therefore we investigated the potency of monoclonal anti-IGF-1R antibody, A12, to enhance radiation response in upper respiratory tract cancers.Methods and Materials
Cell lines were assessed for IGF-1R expression and IGF1-dependent response to A12 or radiation using viability and clonogenic cancer cell survival assays. In vivo response of tumor xenografts to 10 or 20 Gy and A12 (0.25–2 mg × 3) was assessed using growth delay assays. Combined treatment effects were also analyzed by immunohistochemical assays for tumor cell proliferation, apoptosis, necrosis, and vascular endothelial growth factor expression at Days 1 and 6 after start of treatment.
Results
A12 enhanced the radiosensitivity of HN5 and FaDu head-and-neck carcinomas in vitro (p < 0.05) and amplified the radioresponse of FaDu xenografts in a dose-dependent manner, with enhancement factors ranging from 1.2 to 1.8 (p < 0.01). Immunohistochemical analysis of FaDu xenografts demonstrated that A12 inhibited tumor cell proliferation (p < 0.05) and vascular endothelial growth factor expression. When A12 was combined with radiation, this resulted in apoptosis induction that persisted until 6 days from the start of treatment and in increased necrosis at Day 1 (p < 0.01, respectively). Combined treatment with A12 and radiation resulted in additive or subadditive growth delay in H460 or A549 xenografts, respectively.
Conclusions
The results of this study strengthen the evidence for investigating how anti-IGF-1R strategies can be integrated into radiation and radiation-cetuximab regimen in the treatment of cancer of the upper aerodigestive tract cancers.