摘要
OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA)in Glioblastoma multiforme(GBM,WHO gradeⅣastrocytoma).METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM.Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM.Western blotting and siRNA transfection were carried out to check signaling pathway induced by WA.RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro.WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad,and arrested GBM cells at G2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation.In addition,p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim.CONCLUSION WA arrested GBM cells at G2/M phase and triggered the intrinsic apoptosis through p21-Bad axis.
OBJECTIVE To explore the efficacy and mechanism of withaferin A（WA） in Glioblastoma multiforme（GBM, WHO grade Ⅳ astrocytoma）. METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM. Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM. Western blotting and si RNA transfection were carried out to check signaling pathway induced by WA. RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro. WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad, and arrested GBM cells at G2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation. In addition, p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim. CONCLUSION WA arrested GBM cells at G2/M phase and triggered the intrinsic apoptosis through p21-Bad axis.
出处
《中国药理学与毒理学杂志》
CAS
北大核心
2019年第9期696-697,共2页
Chinese Journal of Pharmacology and Toxicology
基金
China Postdoctoral Science Foundation(2018M640093)
National Natural Science Foundation of China(81803584
81573454)
CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007)
National Science and Technology Major Project of China(2018ZX09711001-005-025)
作者简介
Corresponding author:WANG Jin-hua,Email:wjh@imm.ac.cn;Corresponding author:DU Guan-hua,Email:dugh@imm.ac.cn.
