Perifosine regulates human brain glioma U251 cell proliferation, apopto-sis and autophagy through suppression of PI3 K/Akt pathway / 中国病理生理杂志

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.

Caudatin sensitizes TRAIL-induced HepG2 cell apoptosis / 中国病理生理杂志

AIM:To determine whether caudatin , a C21 steroidal aglycone , enhances tumor necrosis factor-re-lated apoptosis-inducing ligand ( TRAIL)-associated HepG2 cell apoptosis .METHODS:Cell growth inhibition was deter-mined by MTT assay and cell colony formation assay .The TUNEL apoptosis detection kit was used to analyze cell apopto-sis, and the protein expression was examined by Western blotting .RESULTS:Combination of caudatin with TRAIL signi-ficantly reduced cell proliferation and increased the apoptotic rate of HepG 2 cells compared with the use of each agent alone.This was evidenced by marked increases in caspase-3, caspase-7, caspase-9 and PARP cleavages in the cells treated with caudatin and TRAIL-compared with control group .Combination of caudatin with TRAIL also led to the strong suppres-sion of survivin .CONCLUSION:Caudatin synergizes HepG 2 cells to TRAIL-induced apoptosis by promoting the cleava-ges of caspase-3, caspase-7, caspase-9 and PARP and inhibiting the expression of survivin .