Perifosine regulates human brain glioma U251 cell proliferation, apopto-sis and autophagy through suppression of PI3 K/Akt pathway
10.3969/j.issn.1000-4718.2016.04.011
- VernacularTitle:Perifosine通过抑制PI3 K/Akt途径调节人胶质瘤U251细胞增殖、凋亡与自噬
- Author:
Ruotong LI
;
Li WANG
;
Ting CAO
;
Shengwen CHEN
;
Hongrong FEI
;
Fengze WANG
- Publication Type:Journal Article
- Keywords:
Perifosine;
Akt;
Glioma;
Apoptosis;
Autophagy
- From:
Chinese Journal of Pathophysiology
2016;32(4):644-650
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of perifosine, an inhibitor of protein kinase B ( PKB/Akt) , on the cell cycle, apoptosis and autophagy in human brain glioma U251 cells, and to determine the relationship between perifos-ine-induced autophagy and apoptosis of glioma.METHODS:The cell growth inhibition was determined by MTT assay. The cell cycle distribution of U251 cells was examined by flow cytometry.The cell apoptosis was analyzed by Annexin V-FITC apoptosis detection kit.The protein expression of P21, P27, cyclin B1, caspase-9 and PARP was examined by Wes-tern blot analysis.The distribution and expression of LC3-Ⅱ, an autophagy marker, was observed to determine the effect of perifosine-induced autophagy.RESULTS:Perifosine inhibited the cell viability in a dose-dependent manner.In perifos-ine-treated U251 cells, the cell cycle was arrested in G2 phase and the expression of cyclin B1 was inhibited.Perifosine in-duced apoptosis of U251 cells through activation of caspase-9 cleavage, PARP cleavage and survivin inhibition.In addi-tion, suppression of autophagy by chloroquin, an inhibitor of autophagy, increased the number of apoptotic cells.CON-CLUSION:Perifosine inhibits cell proliferation and triggers apoptosis and autophagy in human U251 cells.Blocking auto-phagy magnifies perifosine-induced glioma cell apoptosis.
