title: Detection of microRNA-200b may predict the inhibitory effect of gefitinib on non-small cell lung cancer and its potential mechanism.
abstract: The present study aimed to investigate the association and underlying mechanisms between microRNA-200b level and the inhibitory effect of gefitinib on non-small cell lung cancer. In total, 100 patients (43 males and 57 females; median age, 63 years) with advanced non-small cell lung cancer (NSCLC) were selected. All patients were administered with gefitinib orally (250 mg/day) and the effect of gefitinib was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines. Tumor tissue and plasma samples were collected prior to and subsequent to therapy. The microRNA-200b levels in tissues and plasma were determined by quantitative polymerase chain reaction (PCR). A549 cells were culturedin vitroand transfected with microRNA-200b mimic. Using Cell Counting Kit-8 assay, the proliferation inhibition detected was induced by 0.1 µM gefitinib in transfected or non-transfected A549 cells. Cell apoptosis and cell cycle progression were analyzed by flow cytometry and the migration of cells was observed by Transwell assay. In addition, mRNA and protein levels of insulin-like growth factor 1 receptor (IGF-1R), protein kinase B (AKT) and extracellular signal-related kinase (ERK), together with the phosphorylation of AKT and ERK in A549 cells, were determined by quantitative PCR and western blot analysis, respectively. The microRNA-200b levels in gefitinib-insensitive patients were decreased compared with gefitinib-sensitive patients. Transfection with microRNA-200b mimic increased the gefitinib induced proliferation inhibition, apoptosis and cell cycle arrest in A549 cells. Also, transfection with microRNA-200b mimic increased the migration inhibitory effect of gefitinib on A549 cells. Decreased IGF-1R expression together with reduced phosphorylation of AKT and ERK were observed following transfection of A549 cells with the microRNA 200b mimic. In conclusion, detection of microRNA-200b may predict the inhibitory effect of gefitinib on NSCLC. Upregulation of microRNA-200b led to the elevated sensitivity of glioma cells to gefitinib, and this effect may be explained as microRNA-200b being able to inhibit the expression of IGF-1R, thereby reducing the activation of downstream phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling pathways.
authors.affiliation: Department of Medical Laboratory Center, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Laboratory Center, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Medical Laboratory Center, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Bangyun
authors.initials: B
authors.lastname: Tan
authors.affiliation: Department of Medical Laboratory Center, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory Center, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
authors.forename: Baojin
authors.initials: B
authors.lastname: Chen
keywords: IGF-1R; gefitinib; microRNA; non-small cell lung cancer