GW4869 can inhibit epithelial-mesenchymal transition promoted by extracellular HSP90α in EGFR-mutated NSCLC cells

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with the high morbidity and mortality in the world. Meanwhile, the acquired drug resistance against EGFR-mutated NSCLC is increasingly serious. HSP90α might play critical roles in NSCLC, but the effect of GW4869 on extracellular HSP90α remains unclear. We collected plasma samples from 22 NSCLC and 10 healthy individuals, and measured the plasma HSP90α levels by ELISA. Western blot was used to detect the levels of HSP90α, E-cadherin, N-cadherin, and Vimentin in HCC827 and PC9 cells. We found that extracellular HSP90α was upregulated in NSCLC mutated patients and accelerated epithelial-mesenchymal transition (EMT) and invasion/migration capacity in EGFR-mutated NSCLC cells. Meanwhile, we also confirmed that GW4869 inhibited the expression of eHSP90α, EMT and invasion/migration abilities in HCC827 and PC9, and enhanced the antitumor activity of gefitinib in BALB/C nude mice in vivo. These studies suggest that GW4869 can inhibit epithelial-mesenchymal transition promoted by extracellular HSP90α in non-small cell lung cancer, which provides new strategies for delaying the development of acquired resistance to gefitinib for EGFR-mutated NSCLC.