Background: Cyclophilin A (CypA) is associated with metastasis in diverse cancers; however, its role in lung cancer metastasis and the underlying mechanisms remain poorly understood. Our study investigated the effect of CypA on non-small cell lung cancer (NSCLC) metastasis in vitro and in vivo to determine its mechanisms.
Methods: In this study, A549 and H1299 cell lines with downregulated and overexpressed CypA, respectively, were constructed by lentivirus transfection of NSCLC cells. in vitro experiments, including wound healing and transwell assays and Western blotting, showed that CypA promoted cancer cell migration and epithelial-mesenchymal transition in NSCLC. Lung metastasis mouse models were used for the first time to confirm that CypA promoted NSCLC metastasis in vivo. The p38 inhibitor SB203580 was used to show that p38 MAPK is involved in CypA-mediated NSCLC metastasis.
Results: Wound healing and transwell assays showed that the migration of both A549 and H1299 cells decreased in the CypA downregulated group and increased in the CypA overexpressed group. CypA also positively promoted the expression of epithelial-mesenchymal transition-relevant proteins. Results of mouse models confirmed that the tumor metastasis rate was much higher in the CypA overexpressed than in the CypA downregulated group. In addition, SB203580 inhibited NSCLC cell migration significantly in the CypA overexpressed group, while the difference in the CypA downregulated group was not significant.
Conclusions: In conclusion, this study demonstrated that CypA promotes NSCLC cancer metastasis via p38 MAPK.
Keywords: Cyclophilin A (CypA); metastasis; non-small cell lung cancer (NSCLC); p38 MAPK.
© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.