Overexpression of ID1 mediates resistance to osimertinib in T790M positive non-small cell lung cancer through epithelial-mesenchymal transition

Abstract

Objective To analyzed the effect of ID1 overexpression on osimertinib resistance to T790M positive non-small cell lung cancer (NSCLC). Methods We established drug resistant cell line H1975/OR from osimertinib sensitive cell line H1975. Protein alterations of ID1 and Epithelial mesenchymal transition (EMT) were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA. ID1 silencing and overexpression was used to investigate the effect of related gene on osimertinib resistance. Cell Counting Kit-8 (CCK8) was used to assess proliferation rate of ID1 differently expressed cells. Cell cycle and apoptosis was compared using flow cytometry. Results In our study, we found that in osimertinib resistant NSCLC cells, the expression level of EMT related protein E-cadherin was lower than that of sensitive cells, while the expression level of ID1 and vimentin was higher than that of sensitive cells. ID1 expression level was closely related to E-cadherin and vimentin both in osimertinib sensitive and resistant cells. Alteration of ID1 expression in H1975/OR cells could change the expression of E-cadherin. Downregulating ID1 expression of H1975/OR cells could promote the apoptosis induced by osimertinib and block cell cycle at G1/G0 stage. Our study indicated that ID1 may induce EMT in T790M positive NSCLC, which mediates drug resistance of osimertinib. Conclusions Our study reveal the mechanism of ID1 mediated resistance to osimertinib in T790M positive NSCLC through EMT, which may provide new ideas and methods for treatment of EGFR mutated NSCLC after osimertinib resistance.