Inhibition of insulin-like growth factor 1 receptor by CP-751,871 radiosensitizes non-small cell lung cancer cells

Tsutomu Iwasa, Isamu Okamoto, Minoru Suzuki, Erina Hatashita, Yuki Yamada, Masahiro Fukuoka, Koji Ono, Kazuhiko Nakagawa

Research output: Contribution to journalArticle

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Abstract

Purpose: Therapeutic strategies that target the insulin-like growth factor I receptor (IGF-1R) hold promise for a wide variety of cancers. We have now investigated the effect of CP-751,871, a fully human monoclonal antibody specific for IGF-IR, on the sensitivity of human non-small cell lung cancer (NSCLC) cell lines to radiation. Experimental Design: The radiosensitizing effect of CP-751,871 was evaluated on the basis of cell death, clonogenic survival, and progression of tumor xenografts. Radiationinduced damage was evaluated by immunofluorescence analysis of the histone γ-H2AX and Rad51. Results: A clonogenic survival assay revealed that CP-751,871 increased the sensitivity of NSCLC cells to radiation in vitro. CP-751,871 inhibited radiation-induced IGF-IR signaling, and potentiated the radiation-induced increases both in the number of apoptotic cells and in the activity of caspase-3. Immunofluorescence analysis of the histone γ-H2AX and Rad51 also showed that CP-751,871 inhibited the repair of radiationinduced DNA double-strand breaks. Finally, combination therapy with CP-751,871 and radiation delayed the growth of NSCLC tumor xenografts in nude mice to a greater extent than did either treatment modality alone. Conclusions: These results show that CP-751,871 sensitizes NSCLC cells to radiation both in vitro and in vivo, and that this effect of CP-751,871 is likely attributable to the inhibition of DNA repair and enhancement of apoptosis that result from attenuation of IGF-IR signaling. Combined treatment with CP-751,871 and radiation thus warrants further investigation in clinical trials as a potential anticancer strategy.

Original languageEnglish
Pages (from-to)5117-5125
Number of pages9
JournalClinical Cancer Research
Volume15
Issue number16
DOIs
Publication statusPublished - Aug 15 2009
Externally publishedYes

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Somatomedin Receptors
Non-Small Cell Lung Carcinoma
Radiation
Heterografts
Histones
Fluorescent Antibody Technique
Radiation-Sensitizing Agents
figitumumab
Neoplasms
IGF Type 1 Receptor
Survival
Double-Stranded DNA Breaks
Therapeutics
Nude Mice
Caspase 3
DNA Repair
Cell Death
Research Design
Cell Count
Monoclonal Antibodies

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

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Inhibition of insulin-like growth factor 1 receptor by CP-751,871 radiosensitizes non-small cell lung cancer cells. / Iwasa, Tsutomu; Okamoto, Isamu; Suzuki, Minoru; Hatashita, Erina; Yamada, Yuki; Fukuoka, Masahiro; Ono, Koji; Nakagawa, Kazuhiko.

In: Clinical Cancer Research, Vol. 15, No. 16, 15.08.2009, p. 5117-5125.

Research output: Contribution to journalArticle

Iwasa, Tsutomu ; Okamoto, Isamu ; Suzuki, Minoru ; Hatashita, Erina ; Yamada, Yuki ; Fukuoka, Masahiro ; Ono, Koji ; Nakagawa, Kazuhiko. / Inhibition of insulin-like growth factor 1 receptor by CP-751,871 radiosensitizes non-small cell lung cancer cells. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 16. pp. 5117-5125.
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AU - Yamada, Yuki

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