Imperatorin increased sensitivity of lung cancer CD133 +cell subsets to gefitinib by down-regulating c-met expression / 中国病理生理杂志

ABSTRACT

AIM:To investigate the role of imperatorin in reversing the resistance of the PC 9 CD133+cell sub-sets to gefitinib.METHODS:MTT assay was performed to evaluate the viability of PC 9 cells treated with imperatorin and gefitinib.The expression of c-met, activation of caspases and phosphorylation of epidermal growth factor receptor (EGFR), PI3K and AKT in the PC9 cells treated with imperatorin and gefitinib were determined by Western blot .The percentage of CD133 +cell subsets population and the apoptotic rate of the PC 9 cells treated with imperatorin and gefitinib were analyzed by flow cytometry .RESULTS:The sensitivity of the PC 9 CD133 +cell subsets to gefitinib was significantly lower than that of the PC9 CD133 -cell subsets.Treatment with gefitinib alone significantly inhibited the protein levels of EGFR /PI3K/AKT in the PC9 CD133 -cell subsets but not the PC 9 CD133 +cell subsets .Treatment with gefitinib alone increased the percentage of CD133 +cell subsets population in the PC9 cells.However, combination of gefitinib with imperatorin signifi-cantly inhibited the enrichment of CD 133 +cell subsets population .Imperatorin down-regulated c-met expression , sugges-ting the c-met was the target of imperatorin in the PC9 CD133 +cell subsets.The results of MTT assay, Western blot analy-sis and flow cytometry indicated that imperatorin increased the gefitinib induced inhibition of PI 3K/AKT protein levels by down-regulating the expression of c-met, which subsequently induced the cleavage of caspases and apoptosis in the PC 9 CD133 +cell subsets.CONCLUSION:Imperatorin increases the sensitivity of lung cancer CD 133 +cell subsets to gefitinib by down-regulating the expression of c-met, and the synergistic anti-tumor effect exists between imperatorin and gefitinib .