The Effect of STAT3 Activation on Icotinib Sensitivity in Mon-small Cell Lung Cancer Cells with EGFR Mutation

Wang Jinyao; Wang Xiaoli; Che Xiaofang; Hu Xuejun

Abstract：Objective This study aims to use epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer cell lines to explore the factors affecting the icotinib sensitivity and their mechanisms.Methods The effect of icotinib on the proliferation of PC9,HCC827 and A549 cells was measured using MTT assay;protein expression was determined by Western Blot;real-time fluo-rescence quatifative PCR(real-time PCR)was used to dctect the ectinib hydrochloride on the expression level of interleakin-6(IL-6)messenger RNA(mRNA).The experiment was repeated at least three times.The data were expressed as mean±standard devia-tion.SPSS 17.0 software was used to conduct t test for the difference between the two groups of data.Results(1)Icotinib signifi-cantly inhibited the proliferation of EGFR-mutated lung cancer cells PC9 and HCC 827;(2)icotinib could inhibit the phosphoryla-tion level of EGFR,AKT,ERK in PC9 and HCC827 cell;(3)the phosphorylation level of STAT3 was significantly increased with icotinib treatment in PC9 cell,but not in HCC827 cells;(4)icotinib up-regulated the expression of IL-6 mRNA in PC9 cell,but had no effect on HCC827 cells;(5)STAT3 inhibitor or STAT3 siRNA could not affect the activation of AKT and ERK;(6)inhibi-tion of STAT3 activation could enhance sensitivity of icotinib PC9 cells.Conclusion Icotinib can inhibit the proliferation of tumor cells by inhibiting the activation of EGFR and its downstream phosphatidylinositol 3-kinase/AKT and MAPK/ERK signaling pathways in EGFR mutant non-small cell lung cancer;however,in some non-small cell lung cancers,icotinib may reduce the sensitivity of tumor cells to icotinib by up-regulating the expression of IL-6 mRNA and activating STAT3 signaling pathway.