To investigate the effects of lycorine (LYC) on the proliferation and apoptosis of acute promyelocytic leukemia (APL) cells by regulating the phosphatase and tensin homolog deleted on chromosome ten (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway.

Human APL cells (NB4) were treated with 1.0-32.0 μmol·L^-1 LYC, the cell viability was detected, and the LYC experimental concentration was screened. NB4 cells were divided into group A (control group), group B, group C, group D (lycorine low concentration group, medium concentration group, high concentration group), group E (high concentration lycorine+PI3K activator 740 Y-P group). Except for the control group, groups B, C, and D were treated with 4.0, 8.0 and 16.0 μmol·L^-1 lycorine, respectively, for 24 hours. Group E was treated with 16.0 μmol·L^-1 lycorine combined with 25.0 μmol·L^-1 740 Y-P for 24 hours. Cell proliferation, apoptosis, invasion, migration, and cell cycle status were detected, and the expression of related proteins was detected.

After treatment with concentrations of 4.0, 8.0 and 16.0 μmol·L^-1 of lycorine, the survival rate of NB4 cells prominently decreased, therefore, they were used for subsequent experiments. The colony formation numbers of NB4 cells in group A, group B, group C, group D and group E were 151.38±16.42, 117.15±12.78, 81.04±8.36, 56.17±6.05 and 105.02±10.64, respectively. The scratch healing rates were (89.62±9.15) %, (72.57±7.45)%, (55.34±5.83)%, (36.78±3.72)% and (65.59±6.58)%, respectively. The number of cell invasion was (168.27±17.82), (132.69±14.39), (90.58±9.25), (61.64±6.37) and (110.59±12.27), respectively. The proportion of cells in S phase was (46.17±4.71)%, (35.18±3.56)%, (28.20±3.13)%, (20.52±2.16)% and (32.01±3.32)%, respectively. The percentages of cells in G₂/M phase were (24.68±2.56)%, (19.34±1.97)%, (15.62±1.55)%, (11.15±1.23)% and (17.03±1.89)%, respectively. The levels of cyclin dependent kinase 1 (CDK1) were 0.95±0.09, 0.74±0.07, 0.50±0.05, 0.32±0.03 and 0.63±0.06, respectively. The levels of matrix metalloproteinase 2 (MMP-2) were 1.14±0.11, 0.83±0.08, 0.56±0.05, 0.37±0.03 and 0.69±0.06, respectively. The levels of matrix metalloproteinase 9 (MMP-9) were 0.94±0.09, 0.70±0.07, 0.47±0.04, 0.26±0.02 and 0.55±0.05, respectively. The phosphorylated phosphatidylinositol 3-kinase (p-PI3K)/PI3K were 0.86±0.08, 0.71±0.07, 0.45±0.04, 0.26±0.02 and 0.55±0.05, respectively. The expression levels of phosphorylated protein kinase B (p-AKT)/AKT were 0.91±0.09, 0.78±0.07, 0.53±0.05, 0.31±0.03 and 0.69±0.06, respectively. The apoptosis rates were (2.23±0.26)%, (17.41±1.82)%, (26.34±2.75)%, (39.62±4.05)% and (21.58±2.27)%, respectively. The proportion of cells in G₀/G₁ phase was (29.15±3.06)%, (45.48±4.67)%, (56.18±5.73)%, (68.33±6.88)% and (50.96±5.01)%, respectively. The levels of Bcl-2 associated X protein (Bax) were 0.26±0.02, 0.41±0.04, 0.72±0.07, 0.98±0.09 and 0.66±0.06, respectively. The levels of PTEN were 0.32±0.03, 0.45±0.04, 0.74±0.07, 0.96±0.09 and 0.61±0.06, respectively. Group B, group C, group D compared with group A, group E compared with group D, the above indicators were statistically significant (P<0.05). After NK cells were co-cultured with NB4 cells, compared with the A group, the cell killing rate of B, C and D groups increased (P<0.001). Compared with the D group, the cell killing rate of E group decreased (P<0.001).

Lycorine inhibited APL cells with up-regulation of PTEN expression and inhibition of PI3K/AKT pathway, and its effect is dependent on PI3K/AKT pathway.