Notch-1 Confers Chemoresistance in Lung Adenocarcinoma to Taxanes through AP-1/microRNA-451 Mediated Regulation of MDR-1

摘要: We previously demonstrated that expression of Notch-1 is associated with poor prognosis in lung adenocarcinoma (LAD) patients. The aim this study to reveal whether was Taxanes-resistant LAD and, the underlying mechanisms. collected 39 patients advanced treated Taxanes and found positive closely related lymph node metastasis, recurrence poorer prognosis, acts as an independent prognostic factor by multivariate analysis Cox regression model. Then, using Docetaxel (DTX)-resistant cell lines we established previously, contributes resistance cells DTX vitro, inhibition sensitizes vivo. further mediates chemoresistance response strengthens proliferation capacity partially through negative regulation miR-451 transcription AP-1. Moreover, MDR-1 a direct target influences cells. Taken together, our data revealed novel Notch-1/AP-1/miR-451/MDR-1 signaling axis, suggested new therapeutic strategy combining Notch inhibitors treat DTX-resistant LAD.