Abstract: Objective The aim of this study was to investigate the effects of β-elemene on the biological behavior of endometrial cancer Ishikawa cells and its mechanism of action. Methods Different concentrations(0,50,100,150,200,250,300 μg/mL)of β-elemene were used to treat Ishikawa cells.The cell viability was measured using the CCK-8 assay to calculate the half-maximal inhibitory concentration(IC₅₀)of β-elemene and to determining low,medium,and high treatment concentrations.A 0 μg/mL of β-elemene was set up a blank control group and 2 μg/mL of cisplatin for a positive control group.The apoptotic rate was detected using Annexin V-FITC/PI double staining.The scratch wound healing assay and Transwell assay were used to detect the abilities of cell migration and invasion.Western blot was performed to evaluate the expression of PI3K/Akt/mTOR signaling pathway related proteins in Ishikawa cells. Results β-Elemene significantly inhibited the proliferation of Ishikawa cells in a dose-dependent manner.The IC₅₀ values of β-elemene at 24 and 48 hours were 168.9 μg/mL and 157.1 μg/mL,respectively.β-Elemene induced apoptosis in Ishikawa cells and after treatment with β-elemene at 0,85,170,and 255 μg/mL for 24 hours,the apoptotic rates of Ishikawa cells were(9.41±0.52)%,(16.67±0.25)%,(21.27±0.30)% and(25.55±0.89)%,respectively.There was a statistically significant difference in multiple comparisons between groups(P＜0.001).β-Elemene inhibited the migration and invasion ability of Ishikawa cells,and the inhibitory effects increased with concentration(P＜0.001).In addition,β-elemene reduced the levels of PI3K,p-PI3K,mTOR and p-mTOR proteins in Ishikawa cells(P＜0.05),and the expression of p-PI3K and p-mTOR proteins showed a significant concentration dependence,and β-elemene at the 255 μg/mL of group showed a significant reduction in the expression of PI3K,p-PI3K,Akt and p-mTOR when compared to the 0 μg/mL of β-elemene group(P＜0.001). Conclusion β-Elemene can inhibit the proliferation,migration,and invasion of endometrial cancer Ishikawa cells,promote their apoptosis,and its mechanism may be related to the inhibitory activation of the PI3K/Akt/mTOR signaling pathway in Ishikawa cells.

Key words: β-Elemene, Endometrial cancer, Ishikawa cells, PI3K/Akt/mTOR signaling pathway