A combination with IGF-1R inhibitior enhances the sensitivity of human non-small cell lung cancer cell line PC9/G to gefitinib / 肿瘤

ABSTRACT

Objective: To observe the effect of gefitinib alone or in combination with AG1024 (a tyrosine kinase inhibitor of insulin-like growth factor-1 receptor) on drug resistance of human non-small cell lung cancer cell line PC9/G with acquired-resistance to gefitinib, and to discuss its possible mechanism. Methods: PC9/G cells were treated with AG1024 or gefitinib alone or in combination, the proliferative activity of PC9/G cells was detected by MTT method, and the efficacy of combination therapy was assessed by median-effects principle. Apoptosis rate of PC9/G cells was examined by flow cytometry. The expression levels of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated-Akt (p-Akt) and the phosphorylated extracellular signal-regulated kinase (p-ERK) in PC9/G cells were detected by Western blotting. Results: PC9/G cells displayed apoptotic features after treatment with AG1024 or gefitinib alone, and the cell proliferation was inhibited to different degrees. The treatment of AG1024 combined with gefitinib had a synergistic effect on the apoptosis and the cell proliferation (P<0.05) of PC9/G cells, as well as the expression levels of p-EGFR, p-Akt and p-ERK proteins were decreased. Conclusion: AG1024 in combination with gefitinib exerts a synergistic effect, which may lead to the proliferation inhibition and the apoptosis enhancement, and eventually increases the sensitivity of human non-small cell lung cancer cell line PC9/G to gefitinib. Copyright© 2011 by the Editorial Board of Tumor.