Reversal And Mechanism Of Acquired Gefitinib Resistance In Non-small Cell Lung Cancer Associated With EMT By Liver X Receptor Agonist GW3965

Aim:We examined whether EMT affects gefitinib resistance in non-small cell lung cancer(NSCLC)cells.Then,we studied whether the relationship between GW3965 and vimentin could relate to gefitinib resistance in NSCLC cells.Methods:Cell viability was detected by CCK-8 assay.Transwell assay was performed to detect the cells' migration abilities.qRT-PCR was applied to measure the expression level of VIM mRNA.Western blot and immunocytochemistry were performed to determine the expression level of vimentin.We analyzed the expression of vimentin in gefitinib combined with GW3965-treated cells.Results:We observed the morphological changes in gefitinib-sensitive and-insensitive cells.We observed that resistance cells acquire a higher migratory ability,as assessed by a transwell migration assay.Compared with HCC827 cells,the VIM expression level was increased.Results also showed that vimentin is markedly up-regulated in gefitinib-resistant cells.The binning of data revealed that the up-regulated vimentin expression was correlated with gefitinib sensitivity.Our previous study has been improved that co-administration of gefitinib and GW3965 resulted in a decrease in cell proliferation and induced the apoptosis.When under the combine treatment of GW3965(5?M)&gefitinib(5?M),cell death rate was increased observably.Additionally,gefitinib leads to increase in the vimentin level intracellular,and GW3965 decreased the vimentin expression level,which was caused by gefitinib in drug-resistance NSCLC cells.Conclusion:In conclusion,these findings suggest that vimentin is related to the sensitivity to gefitinib,and our study provide a useful drug named GW3965 to reverse the gefitinib resistance by inhibiting the expression of vimentin.