Abstract: Abstract   Objective  To investigate the effects and the mechanism of hispidulin on the proliferation of lung carcinoma A549 cell line. Method   After human lung carcinoma cell line A549 was treated with different concentrations of hispidulin, the cellular proliferation was detected by MTT assay. The flow cytometry was used to determine the change of cell cycle in A-549 cells. Western blot was employed to detect the expressions of cyclin D1, CDK4, p21 and p27 in A-549 cells. Immunocytochemistry was used to detect the expression of proliferation cell nuclear antigen in A-549 cells. Result  The proliferation of lung carcinoma cells was inhibited significantly by hispidulin. The cell viability values were (57.30±3.92)%, (43.91±4.32)%, (17.82±2.73)% and (13.20±2.46)% respectively after treatment with the concentrations of hispidulin 15、30、60、120μmol?L-1 for 72h, which were significantly lower than those (96.30±2.08)% in control group (P﹤0.01). Treatment with hispidulin (15 and 30 μmol.L-1) for 24h induced cell cycle arrest at G1/S phase in A-549 cells. Treatment with hispidulin (15、30 and 60μmol.L-1) for 24h in A-549 cells reduced the expression of cyclin D1 and CDK4 proteins and increased levels of p21 protein. The positive expression of proliferation cell nuclear antigen was significantly decreased in A-549 cells treatment with hispidulin (15、30 and 60μmol.L-1) than those of control group (P﹤0.01). Conclusion  Hispidulin can inhibit the proliferation of A-549 cells through changing cell cycle, which may be related to the up-regulated level of p21 and down-regulated levels of cyclin D1 and CDK4.

Key words: Lung neoplasms, cell line, tumor, cell proliferation, Cell cycle, CyclinDl, cyclin-dependent kinase 4, 周期素依赖激酶抑制剂p21