GW4869 Can Inhibit Epithelial-Mesenchymal Transition and Extracellular HSP90α in Gefitinib Sensitive NSCLC Cells

Objective: GW4869 is an exosomal inhibitor. It is necessary to delay the occurrence of gefitinib resistance during non-small-cell lung cancer (NSCLC) treatment. This study aimed to investigate the anti-tumor effects of GW4869 on epithelial-mesenchymal transition (EMT) and expression of extracellular heat shock protein 90 alpha (eHSP90 alpha) that contributes to acquired resisitance. Our study provides a new sight into the treatment of EGFR-mutated NSCLC.Materials and Methods: We performed western blotting to detect levels of EMT and eHSP90 alpha. Wound healing and transwell assays were performed to evaluate the behavioral dynamics of EMT. A nude mouse model of HCC827 was established in vivo. Results: GW4869 inhibited the expression of eHSP90 alpha, EMT, invasion and migration abilities of HCC827 and PC9. GW4869 enhanced sensitivity to gefitinib in BALB/c nude mice bearing tumors of HCC827.Conclusion: These studies suggest that GW4869 can inhibit EMT and extracellular HSP90 alpha, providing new strategies for enhancing gefitinib sensitivity in NSCLC.