OncoTargets and Therapy (Oct 2019)
Bag-1 Silence Sensitizes Non-Small Cell Lung Cancer Cells To Cisplatin Through Multiple Gene Pathways
Abstract
Jiling Lv,1,2 Fang Zhang,3 Congying Zhai,2 Gejin Wang,4 Yan Qu1 1Department of Intensive Care Unit, Affiliated Qingdao Municipal Hospital of Qingdao University, Qingdao 266071, Shandong, People’s Republic of China; 2Department of Respiratory Medicine, The First Hospital of Zibo, Zibo 255200, Shandong, People’s Republic of China; 3Department of Radiotherapy, Yantai Affiliated Hospital of Binzhou Medical University, Yantai 26400, Shandong, People’s Republic of China; 4Department of Nursing, Zibo Vocational Institute, Zibo 255314, Shandong, People’s Republic of ChinaCorrespondence: Yan QuThe Intensive Care Unit, Qingdao Municipal Hospital Affiliated to Qingdao University, 1 Jiaozhou Road, Qingdao 266071, Shandong, People’s Republic of ChinaTel +8613668892506Email [email protected]: B-cell lymphoma-2 (Bcl-2) associated athanogene 1 (Bag-1) is a multifunctional protein, and Bag -1 overexpression is associated with progression, metastasis, and drug resistance in lung cancer. This study assessed the effects of Bag-1 siRNA on sensitization of cisplatin on non-small cell lung cancer (NSCLC) cells.Material and methods: NSCLC A549 cell line was transfected with Bag-1 or negative control siRNA and then treated with cisplatin for cell viability, CCK-8, LDH, and flow cytometry assays. The Ca2+ levels were analyzed using Fluo-3/AM fluorescence staining, and the protein levels were assessed using Western blot analysis.Results: Bag-1 siRNA significantly knocked down Bag-1 expression and inhibited cell invasion versus the negative control siRNA, while Bag-1 silence sensitized cisplatin to induce A549 cells to apoptosis by induction of cell cycle G1 arrest. At protein level, Bag-1 silence reduced the expression ratio of Bcl-2 to Bcl-2 associated X protein (Bax), downregulated activity of the PI3K/AKT and mitogen-activated protein kinase (MAPK) pathways, and potently upregulated the calcium signaling-mediated pathway.Conclusion: This study demonstrated that Bag-1 silencing sensitized A549 to cisplatin to enhance A549 cell apoptosis by modified multiple gene pathways. Further study will evaluate the usefulness of Bag-1 siRNA as a potential targeting therapy for NSCLC.Keywords: bag-1, apoptosis, non-small cell lung cancer, chemotherapy
