The Mechanisms On The Apoptosis Of Glioma Cells Induced By Genistein

Objective: To explore the effects of Genistein on the proliferation and apoptosis of U87 and U251 glioma cells, and to clarify the mechanisms.Method: U87 and U251 cell morphology changes induced by genistein were observed under microscopes; the apoptosis rates of glioma cells were detected by MTT; the apoptosis and cell cycle arrest situations of glioma cell were detected by flow cytometry; related apoptotic protein such as Bax、Bcl-2、 Cyclin B1、Cyclin D1、PI3K-Akt pathway protein、14-3-3θ、human telomerase protein were detected by Western Blot.Results: Compared with the control group, with the concentrations of Genistein for 24 h, 48 h or 72 h increasing, U87 and U251 cell vitality or survival were significantly inhibited. The differences between cell vitality or survival were statistically significant in concentration of Genistein(200, 400, 600 μmol /L)(compared with the control group, *P < 0. 05). With the concentrations of Genistein increasing, the percentage cells in G0-G1 phase were gradually reduced, while cells in G2-M phase wered increased(compared with control group, * * P < 0. 05, the differences were statistically significant). Meanwhile Western Blot results show that with concentrations of Genistein increasing, the protein expressions of Cyclin B1 were gradually reduced. And here were no obvious changes in Cyclin D1. However p21 and p53 were gradually increased. Western Blot results also show that with the concentration of Genistein increasing, there were no obvious changes in the total protein expressions level of PI3 K and Akt, however the protein expression levels of phosphorylation p-PI3 K 、phosphorylation p-Akt and 14-3-3 θwere gradually decreased. At the same time, there was a different trend that the expression of h TERT in cytoplasm increased but in the nuclei declined.Conclusion: 1 、 The proliferation of U87 and U251 glioma cells induced by Genistein have a significant inhibitory effect and Genistein may be the potential role of anti-tumor.2、Genistein could induce U87、U251 cells G2 / M phase arrest by upregulating the protein expression level of p21、p53,inhibiting the protein expression level and the activity of Cyclin B1.3、The reason for glioma cells apoptosis induced by Genistein may be through the inhibition of PI3K-Akt pathway, regulation of the protein expressionof p-Akt level and p-PI3 K level, affection of the protein expression of 14-3-3.Further more, Genistein may regulate the phosphorylation levels of h TERT and promote h TERT shifting from the nucleus to the cytoplasm leading to the inhibition of the activity of telomerase.