Abstract
Small-cell lung cancer (SCLC) represents the progressive form of lung cancer. Patients with SCLC have poor prognosis, partially due to drug resistance. Therefore, understanding the underlying mechanism for drug resistance in SCLC is needed to improve clinical outcomes. The concentrations of heat shock protein 90α (HSP90α) in medium were detected by enzyme-linked immunosorbent assay. The protein levels were detected by Western blot. Cell apoptosis was detected by propidium iodide staining in cell lines or terminal deoxynucleotidyl transferase dUTP nick end labeling staining in tumor sections. Doxorubicin (DOX) was administered into cultured cell lines or intraperitoneally injected into xenograft mouse to induce apoptosis. In SCLC cell lines, either DOX or ABT-737 increased extracellular HSP90α levels, which attenuated the percentage of apoptotic cells. Extracellular HSP90α activated Ak strain transforming (AKT) and β-catenin signaling and inhibited glycogen synthase kinase 3β (GSK3β) signaling. In the xenograft mouse model, extracellular HSP90α promoted tumor development and inhibited apoptosis of tumor cells. Heat shock protein 90α attenuates the efficacy of anticancer drugs in SCLC cells through AKT/GSK3β/β-catenin signaling.