摘要
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.
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.
