Combined inhibition of insulin-like growth factor-1 receptor enhances the effects of gefitinib in a human 
non-small cell lung cancer resistant cell line

Qi,Hui wei; Shen,Zan; Fan,Li hong

doi:10.3892/etm.2011.324

Combined inhibition of insulin-like growth factor-1 receptor enhances the effects of gefitinib in a human non-small cell lung cancer resistant cell line

Authors:
- Hui wei Qi
- Zan Shen
- Li hong Fan
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Affiliations: Department of Respiratory Medicine, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China, Department of Oncology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, P.R. China
Published online on: August 3, 2011 https://doi.org/10.3892/etm.2011.324
Pages: 1091-1095

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Abstract

The type I insulin-like growth factor receptor (IGF-1R) signaling pathway is an important growth-regulatory pathway that is prevalent in a variety of cancer types, including human non-small cell lung cancer (NSCLC). To observe the combined effects of gefitinib and AG1024-induced IGF-1R inhibition on the growth of NSCLC, PC9/G cells, a NSCLC cell line with acquired resistance to gefitinib, were treated with AG1024 and gefitinib, alone or in combination. The proliferative activity of PC9/G cells upon different treatments was assessed by CCK-8, and the median-effects principle was used to assess the effect of the combined treatment. Apoptotic rates of the PC9/G cells for the different treatment groups were analyzed by flow cytometry. The expression of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated-Akt (p-Akt), and phosphorylated extracellular signal-regulated kinase (p-ERK) in PC9/G cells was examined by Western blotting. PC9/G cells exhibited apoptotic features after treatment with AG1024 and gefitinib alone, and their proliferation rates were inhibited to different degrees. The treatment of AG1024 combined with gefitinib resulted in a synergistic effect in inducing apoptosis, inhibiting cell proliferation and decreasing the expression of p-EGFR, p-Akt and p-ERK. In conclusion, combined inhibition of IGF-1R signaling enhances the anti-proliferative and pro-apoptotic effects of gefitinib in NSCLC gefinitib-resistant cells. Moreover, the addition of an anti-IGF-1R strategy to gefitinib treatment may be more effective than a single-agent approach.

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