Role of BCL2-associated athanogene in resistance to platinum-based chemotherapy in non-small-cell lung cancer

摘要

The present study aimed to address the pharmacogenetic role of BAG1 in platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) and in cultured human lung adenocarcinoma A549 cells. A total of 108 NSCLC patients (stages I-IIIA) were treated with a standard chemotherapy regimen of cisplatin plus vinorelbine. Additionally, in vitro cultured A549 cells were treated with cisplatin in the presence or absence of tunicamycin. Cell proliferation was determined by MTT assay and protein levels were assessed via western blot analysis. Patients with BAG1-positive expression were revealed to have a prolonged survival time (progression-free survival, 24.0 months) compared with that of patients without BAG1 expression (21.6 months; chi(2)= 18.018, P< 0.05). Treatment of A549 cells with tunicamycin followed by cisplatin resulted in elevated BAG1 levels. In addition, tunicamycin was found to significantly enhance cisplatin-induced growth inhibition and apoptosis in A549 cells. The results indicate that BAG1 is important in cisplatin-induced cell death in lung adenocarcinoma, suggesting that endoplasmic reticulum stress may promote the sensitivity of NSCLC patients to chemotherapy.