OBJECTIVE: To explore the effects of evodiamine on ovarian cancer cells and the mechanisms underlying such effects.METHODS: Human ovarian cancer cells HO-8910 PM were treated with evodiamine at 0, 1.25,2.5, and 5 μM for 1-4 d. 3-(4,5-Dimethiylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay was used to detect the growth inhibition rate of evodiamine-treated HO-8910 PM cells. The cell cycle was observed via propidium iodide(PI) staining. Apoptosis induction was assessed via Annexin V-fluorescein isothiocyanate/propidium iodide(Annexin V-FITC/PI) double staining assay. To verify the mechanism of apoptosis, caspase-dependent apoptotic pathway-related protein was detected by Western blot analysis. The expression levels of mitogen-activated protein kinase(MAPK)and/or phosphatidylinositol-3-kinase(PI3K)/pro-tein kinase B(Akt) pathway-related proteins were also investigated.RESULTS: Evodiamine significantly inhibited the proliferation of HO-8910 PM cells in a dose- and time-dependent manner. Evodiamine induced G2/M arrest with an increase of cyclin B1 level, and promoted cell apoptosis with a decrease of B cell lymphoma/lewkmia-2(Bcl-2) and an increase of Bcl-2-associated X protein(Bax) level. In addition,evodiamine treatment led to the activation of caspase-8, caspase-9, and caspase-3 and the cleavage of poly(ADP-ribose)-polymerase(PARP). Evodiamine targeted the MAPK and/or PI3K/Akt pathways by reducing the expression and activity of PI3 K, Akt, and extracellular signal-regulated kinase mitogen-activated protein kinase(ERK1/2 MAPK)and the activity of p38 MAPK.CONCLUSION: Evodiamine can inhibit the growth of ovarian cancer cells by G2/M arrest and intrinsic and extrinsic apoptosis. In addition, evodiamine-induced PI3K/Akt, ERK1/2 MAPK, and p38 MAPK signaling may be involved in cell death.