Anticancer mechanism of breviscapine in non-small cell lung cancer A549 cells acts via ROS-mediated upregulation of IGFBP4

Background The overall 5-year survival rate of non-small cell lung cancer (NSCLC) is less than 15% because of multiple drug resistance to chemotherapy and the limitations of early diagnosis. Thus, safe and effective drugs to treat NSCLC are required. The present study aimed to investigate the effects of breviscapine (BVP) on NSCLC cell apoptosis and proliferation, and to study its possible mechanisms. Methods Using the NSCLC A549 cell line and BVP (0, 25, 50, and 100 µM), the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect A549 cell proliferation, and flow cytometry was used to assess cell apoptosis. Insulin-like growth factor binding protein 4 (IGFBP4) levels was assessed using enzyme-linked immunosorbent assays and western blotting. Flow cytometry of hydrogen peroxide and superoxide was used to assess intracellular reactive oxygen species (ROS) generation. Western blotting was used to assess the levels of BCL2-associated X, apoptosis regulator (BAX) and B-cell CLL/lymphoma 2 (BCL2). Quantitative real-time reverse transcription PCR (qRT-PCR) was used to assess IGFBP4 mRNA expression. Results BVP induced apoptosis, inhibited cell proliferation, and increased ROS in A549 cells. Western blotting and qRT-PCR showed that BVP increased IGFBP4 protein and mRNA expressions in A549 cells. Compared with BVP treatment alone, IGFBP4 expression decreased in A549 cells treated with BVP and the ROS scavenger N-acetylcysteine. IGFBP4 overexpression increased BVP-induced proliferation inhibition, while increasing BAX expression and decreasing BCL2 expression. Silencing IGFBP4 had the opposite effects. Conclusions BVP could inhibit the growth of NSCLC A549 cells by promoting apoptosis via ROS-mediated upregulation of IGFBP4.