Human Recombinant IL-17A Enhances The Effects Of Gefitinib In NCI-H1650: A Lung Cancer Cell Line With Resistance To Gefitinib

Objective:EGFR-TKI has been proven to be effective in the treatment of NSCLCpatients who is harboring EGFR activating mutations.However,after12-14months,themajority of them would develop acquired resistance,and the magnitude of tumorregression is variable.This study is to investigate whether IL-17A could reverse theresistance of NCI-H1650to gefitnib.Materials and Methods:The sensitivity of NCI-H1650to gefitinib was determinedby MTT assays.IL-17RA gene expression in NCI-H1650was tested byRT-PCR.NCI-H1650cancer cells were cultured with or without IL-17A (10ng/mL)in the presence of5or10μM gefitinib,the inhibition rate was assessed by MTTassays.Cells were cultured with IL-17A(0,0.1,1,10or100ng/mL),the IL-6geneexpression was determined by real-time PCR at6h,12h,24h and48h. Cancer cellswere also cultured with IL-17A (10ng/mL) alone,the phosphorylation status ofAkt,ERK and NF-κB were measured withWesternblots.Results:The IC50of NCI-H1650to gefitinib was17.87μM,NCI-H1650is insensitiveto gefitinib.RT-PCR results showed that IL-17RA gene is expressed inNCI-H1650.IL-17A could suppress the growth of NCI-H1650in the presence of5or10μM gefitinib.IL-6gene expression was only up-regulated by IL-17A(0.1,1,10or100ng/mL) at6h,IL-17A couldn t induce the expression of IL-6in NCI-H1650at12h,24h and48h.IL-17A could induce the phosphorylation of Akt,but the phosphorylation level of ERK and NF-κB were reduced after IL-17A exposure.Conclusions: These results suggest that human recombinant IL-17A can reverse theresistance of NCI-H1650to gefitnib,and it might result from the balance betweenp-Akt(ser473), p-ERK and p-NF-κB.