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Archive > Volume 22 Issue 4 > 2015,22(4):427-431. DOI:10.3872/j.issn.1007-385X.2015.04.003 Prev Next
Basic Research
c-Met inhibitor reverses HGF-induced resistance to Erlotinib in non-small lung cancer cells with different EGFR gene types
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Abstract:
Objective:To investigate whether c-Met inhibitor SU11274 can reverse resistance to Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), induced by HGF in non-small cell lung cancer cells with different EGFR gene types. Methods: NSCLC cells with different EGFR gene types, including PC9 (EGFR-activating mutant), H292 (EGFR-wild type), and A549 (EGFR-wild type) were utilized in the study. The experiments for each cell line consisted of six different treatment groups: C group (control), H group (HGF), E group (Erlotinib), S group (SU11274), EH group (Erlotinib+HGF), and ESH group (Erlotinib+SU11274+HGF). Their effects on cell survival and apoptosis were measured by MTT assay and flow cytometry (FCM). The activation of c-Met, Stat3, Akt, and Erk1/2 protein were examined by immunoblotting. Results: Erlotinib inhibited growth of the three cells lines in a dose-dependent manner, and the inhibition was effectively blocked by HGF. The presence of SU11274 significantly decreased the survival rates of cells exposed to HGF and Erlotinib (P<0.05). Apoptosis in cells treated with Erlotinib, SU11274, and HGF was also markedly increased compared with these treated with Erlotinib and HGF only (P<0.05). Similarly, the levels of p-Met, p-Stat3, p-Akt, and p-Erk1/2 in the HES group were significantly lower than that in the HE group (P<0.05). Conclusion: SU11274 reversed HGF-induced resistance to Erlotinib in non-small lung cancer cells with different EGFR gene type, likely due to the inhibition of HGF-induced activation of c-Met and its down streams signaling pathways.
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Project Supported:
Project supported by the National Natural Science Foudation of China (No.81160291)
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