Caudatin combined with Gefitinib reversing HGF induced non-small cell lung cancer to EGFR-TKI acquired drug resistance / 中国生化药物杂志

ABSTRACT

Objective To investigate the effect and underlying mechanism of Caudatin combined with Gefitinib on Gefitinib resistance induced by HGF in PC-9.Methods Model of EGFR-TKIs resistance in PC-9 cells was induced by exogenous HGF and co-cultured with MRC-5.Caudatin was tested as a drug resistant modulator to reverse the resistance of Gefitinib in PC-9 cells induced by HGF by MTT assay.Western blot was performed to observe the mechanism of Caudatin combined with Gefitinib reversing the resistance of PC-9 induced by HGF.Results The resistance of gefitinib to PC-9 was induced by exogenous HGF and co-cultured with MRC-5 which could reduce relative inhibitory rate ( P<0.05 ) .Neither caudatin ( 0-32 μM ) or Gefitinib (1μM) alone could significantly inhibit proliferation of PC-9 in the presence of HGF, which could be inhibited in a dose-dependent manner by Caudatin combined with Gefitinib ( P<0.05 ); Caudatin combined with Gefitinib down-regulated the phosphorylation levels of Met and PI3K/Akt simultaneously (P<0.05).Conclusion Caudatin could reverse the drug resistance of Gefitinib in PC-9 induced by HGF, the mechanism of which may be related to the inhibition of Met/PI3K/AKT pathway.