Alpha-1 Antitrypsin Induces Epithelial-to-Mesenchymal Transition, Endothelial-to-Mesenchymal Transition, and Drug Resistance in Lung Cancer Cells

Dong-ming Wu,* Teng Liu,* Shi-hua Deng, Rong Han, Ting Zhang, Jing Li, Ying Xu Clinical Laboratory, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ying Xu Tel +86 02883016723Email yingxu825@126.comPurpose: Alpha-1 antitrypsin (A1AT) is a secreted protein that plays an important role in various diseases. However, the role of A1AT in non-small cell lung cancer is obscure.Materials and Methods: A1AT expression in non-small cell lung cancer was analyzed using quantitative reverse transcription PCR, Western blotting (WB), immunohistochemistry (IHC), and ELISA. WB and IF were used to analyze markers of epithelial-to-mesenchymal transition (EMT), EndoMT, and cancer stem cell (CSC). Transwell and cell wound healing assays were used to analyze migration and invasion abilities. Colony formation and CCK-8 assays were used to analyze cell proliferation following cisplatin treatment.Results: A1AT expression was higher in lung cancer samples than in normal tissues and the increased expression was correlated with poor overall survival of patients. In vitro experiments showed that A1AT overexpressed by plasmid transfection significantly promoted migration, invasion, EMT, EndoMT, stemness, and colony formation in lung cancer cell lines, as opposed to A1AT downregulation by siRNA transfection, which significantly inhibited all these variables.Conclusion: A1AT is a novel therapeutic target and might be associated with tumor metastasis in lung carcinoma.Keywords: epithelial-to-mesenchymal transition, endothelial-to-mesenchymal transition, alpha-1 antitrypsin, non-small cell lung cancer, cisplatin resistance