Abstract: Objective The aim of this study was to investigate whether downregulation of FK506 binding protein 4(FKBP4)could inhibit the malignant progression of non-small cell lung cancer(NSCLC)by blocking the PI3K/Akt/mTOR signaling pathway. Methods NSCLC A549,H1975,H358 and PC-9 cell lines,as well as human bronchial epithelial cells(HBE)were routinely cultured.The expression of FKBP4 in these cells was detected by qRT-PCR,and NSCLC cell lines with the most significant different expression of FKBP4 compared with HBE cells was screened.FKBP4 siRNA and NC siRNA were transfected into A549 cells,which were divided into the si-FKBP4 group and NC group.CCK-8 assay was used to detect the proliferative ability of si-FKBP4 group and NC group,flow cytometry was used to detect the apoptosis rate,scratch healing assay was used to detect the migration ability,Transwell assay was used to detect the invasion ability,and Western blot was used to detect the total and phosphorylation protein expression of PI3K and its downstream effectors Akt and mTOR. Results The expression of FKBP4 in A549 cells,H1975 cells,H358 cells and PC-9 cells were significantly higher than those in HBE cells(P＜0.05),and its expression in A549 cells was the highest(P＜0.001).Downregulation of FKBP4 could inhibit the proliferation,invasion and migration of A549 cells and promote the apoptosis of A549 cells(P＜0.001).In addition,downregulation of FKBP4 also could inhibit the phosphorylation of PI3K,Akt and mTOR,resulting in blocking the PI3K/Akt/mTOR signaling pathway. Conclusion Downregulation of FKBP4 can inhibit the proliferation,invasion and migration of NSCLC cells by blocking the PI3K/Akt/mTOR signaling pathway,and promote the apoptosis of NSCLC cells.

Key words: Non-small cell lung cancer, FK506 binding protein 4, Phosphatidylinositol-3-kinase/protein kinase B/mammalian rapamycin target protein signaling pathway, Proliferation, Apoptosis