To investigate the effect and molecular mechanism of grifolin on the proliferation, transfer, and infiltration of lung cancer (LC) cells. A control group, low grifolin group, midium grifolin group and high grifolin group, anti-miRNA-NC group, anti-miRNA-1251-5p group, grifolin + miRNA-NC
group, and grifolin + miRNA-1251-5p group were established based on LC A549 cells. MTT was employed to detect cellular proliferation inhibition rate; Transwell assay was used to detect cellular transfer and infiltration; Western blot was used to test Cyclin D1, cyclin-dependent kinase inhibitor
1A (p21), matrix metalloproteinase 2 (MMP-2), and matrix metalloproteinase 9 (MMP-9) protein expression; and finally RT-qPCR was employed to test miRNA-1251-5p expression. After treatment with different concentrations of grifolin, an increase in proliferation inhibition rate of A549 cells,
a decrease in migrating and invading cells, a decrease in CyclinD1, MMP-2, and MMP-9 expression, an increase in p21 expression, and a decrease in miRNA-1251-5p expression in a manner of concentration dependence was observed (P < 0.05). Inhibiting miRNA-1251-5p expression led to an
increase in cellular proliferation inhibition rate, a decrease in migrating and invading cells, a decrease in CyclinD1, MMP-2, and MMP-9 expression, and an increase in p21 expression (P < 0.05). Overexpression of miRNA-1251-5p reversed the inhibitory influence of grifolin on the
proliferation, transfer, and infiltration of A549 cells. Grifolin likely inhibits the proliferation, transfer, and infiltration of LC A549 cells by down-regulating miRNA-1251-5p.