Study of Inhibition of Fudosteine on Mucin MUC1 and MUC5AC in Lung Cancer Cells

OBJECTIVE To explore the regulatory effects of the mucoactive agent fudosteine on highly expressed mucins MUC1 and MUC5AC in lung cancer cells. METHODS Firstly, the molecular docking technology was used to dock fudosteine, the original ligand and the positive drug with MUC1 and MUC5AC proteins, and the binding energy value and the molecule-protein interaction activity of the docking pocket were preliminarily obtained. Then PCR and ELISA experiment were used to verify the regulatory effect of different concentrations of fudosteine on TNF-a-induced high expression of MUC1 and MUC5AC in vitro from the cellular level. RESULTS Molecular docking results showed that fudosteine spontaneously bound to MUC1 and MUC5AC, and that fodosteine binds more tightly to MUC1 than to MUC5AC. The results of cell verification showed that the high expression of MUC1 and MUC5AC in lung cancer A549 cells or the high expression of MUC1 in NCI-H292 cells stimulated by TNF-a could be inhibited by 1 mmol·L^-1 to 10 mmol·L^-1 of fudosteine, and the effect of lowering MUC1 protein expression was better than that of MUC5AC protein. Fudosteine was first found to block the expression of MUC1 protein in lung cancer A549 cells in a concentration-dependent way. CONCLUSION Fudosteine can inhibit the expression of MUC1 and MUC5AC in A549 and the expression of MUC1 in NCI-H292 lung cancer cell, and this study supplies a theoretical basis for intervening the metastasis and invasion of lung cancer cells and providing theoretical basis for the clinical treatment of patients with mucinous lung cancer.