没药甾酮下调PI3K/Akt通路增强替莫唑胺抗脑胶质瘤细胞增殖作用

Guggulsterone enhanced inhibitory effect of temozolomide on glioblastoma cells through PI3K/Akt pathway

目的 探讨没药甾酮增强替莫唑胺抗人脑胶质瘤细胞增殖的作用及机制。方法分别用CCK-8、Hoechst 33342染色和流式细胞术、Western blot检测没药甾酮、替莫唑胺单药及联合对人脑胶质瘤U251细胞增殖、凋亡、PI3K/Akt通路活性,以及凋亡相关蛋白Bcl-2、Bax表达影响。结果与替莫唑胺(1~400 μmol·L^-1)单药组相比,没药甾酮(30 μmol·L^-1)联合替莫唑胺(1~400 μmol·L^-1)明显增强对人脑胶质瘤U251细胞的抗增殖作用;与替莫唑胺(400 μmol·L^-1)单药组相比,没药甾酮(30 μmol·L^-1)联合替莫唑胺(400 μmol·L^-1)明显增强对人脑胶质瘤U251细胞的凋亡诱导作用(P<0.01);与替莫唑胺(400 μmol·L^-1)单药组相比,没药甾酮(30 μmol·L^-1)联合替莫唑胺(400 μmol·L^-1)明显下调PI3K、p-PI3K p110、p-Akt(Ser473)和Bcl-2的表达。结论没药甾酮可通过下调PI3K/Akt通路,增强替莫唑胺对人脑胶质瘤细胞U251的增殖抑制作用。

Aim To investigate the mechanism of the combination of guggulsterone and temozolomide in inhibiting human glioblastoma cells.Methods Glioblastoma U251 cells were treated with guggulsterone and temozolomide alone or in combination.Cell proliferation was determined by CCK-8.The level of apoptosis was evaluated by Hoechst 33342 staining and flow cytometry.PI3K/Akt pathway activity and the level of apoptosis-associated proteins Bcl-2 and Bax expression were analysed by Western blot.Results Guggulsterone(30 μmol·L^-1) significantly enhanced the inhibitory effect of temozolomide(1~400 μmol·L^-1) on U251 cells,as compared with temozolomide treatment alone.Guggulsterone(30 μmol·L^-1) significantly enhanced the effect of temozolomide(400 μmol·L^-1)-induced apoptosis on U251 cells,as compared with temozolomide treatment alone(P<0.01).Furthermore,guggulsterone(30 μmol·L^-1) significantly down-regulated the expression of PI3K,p-PI3K p110,p-Akt(Ser473) and Bcl-2,as compared with temozolomide treatment alone.Conclusion Guggulsterone enhances the inhibitory effect of temozolomide on human glioblastoma U251 cells through PI3K/Akt pathway.