To investigate the effects of baicalein combined with 5-fluorouracil (5-FU) on the proliferation, apoptosis and migration of H446 cells, and to explore the sensitization mechanism.

Lung cancer H466 cells were allocated into blank, control, experimental and combination groups. The blank group was treated with 10 μmol·L^-1 dimethyl sulfoxide, the control group with 20 μmol·L^-1 baicalein, the experimental group with 20 μmol·L^-1 5-FU, and the combination group with 10 μmol·L^-1 baicalein plus 10 μmol·L^-1 5-FU. Cell viability was determined using the cell counting kit-8 assay. Apoptosis and reactive oxygen species (ROS) levels were analyzed by flow cytometry. Cell migration was evaluated with Transwell assays, and alterations in mitogen-activated protein kinase (MAPK) pathway protein expression were examined by Western blotting.

After 24 h of incubation, cell viability in blank, control, experimental and combination groups were (114.34±2.88)%, (79.87±3.48)%, (57.66±1.82)% and (40.31±2.73)%, respectively; the corresponding apoptosis rates were (14.47±1.36)%, (33.94±4.33)%, (49.20±3.82)% and (49.17±2.13)%; and cell migration rates were (8.43±1.94)%, (11.25±1.55)%, (26.74±3.31)% and (68.83±4.32)%. Compared with control group, the above indexes of experimental group and combined group were significantly increased, and combined group were significantly higher than experimental group (all P<0.01). After adding ROS scavenger NAC to combination group, the apoptosis rates of blank group, control group, experimental group, combination group and combination group+NAC were (7.82±0.94)%, (12.31±2.13)%, (33.48±4.92)%, (52.42±3.17)% and (30.39±2.72)%, respectively; the cell migration rates were (4.36±0.54)%, (4.92±0.71)%, (31.43±3.14)%, (52.64±5.26)% and (27.61±3.52)%, respectively. Compared with combined group, the above indexes of combined group+NAC were significantly decreased (all P<0.01). The relative expression levels of p-JNK protein in blank, experimental, control, combination and combination group+NAC were 0.78±0.05, 0.70±0.04, 0.73±0.03, 0.98±0.02 and 0.73±0.05, respectively; the relative expression levels of p-p38 were 0.56±0.02, 0.51±0.03, 0.60±0.04, 0.76±0.06 and 0.54±0.03, respectively; the relative expression levels of p-ERK were 0.34±0.03, 0.30±0.04, 0.28±0.04, 0.18±0.03 and 0.33±0.05, respectively. The relative expression levels of p-JNK and p-p38 protein in combination group were significantly higher than those in control group, and the relative expression levels of p-ERK protein were significantly lower (all P<0.01); the relative expression levels of p-JNK and p-p38 low protein in combined group+NAC were significantly decreased, while the relative expression levels of p-ERK protein were significantly increased (all P<0.01).

The combination of baicalein and 5-FU can enhance the inhibitory effect on proliferation, induce apoptosis, and suppress migration in H446 cells by upregulating ROS levels, activating the JNK and p38 pathways, and inhibiting the ERK pathway.