本研究探讨葛根有效成分对恶性白血病可能的凋亡诱导作用及其分子机制。采用葛根总黄酮(flavonoids of puerarin,PR)处理人早幼粒细胞白血病(APL)细胞株NB4,用MTT法检测细胞增殖抑制率;FITC-Annexin V/PI双染法检测细胞凋亡率;实时定量...本研究探讨葛根有效成分对恶性白血病可能的凋亡诱导作用及其分子机制。采用葛根总黄酮(flavonoids of puerarin,PR)处理人早幼粒细胞白血病(APL)细胞株NB4,用MTT法检测细胞增殖抑制率;FITC-Annexin V/PI双染法检测细胞凋亡率;实时定量PCR检测pml/rarα、bcl-2、survivin基因表达;Western blot检测JNK、p38MAPK、FasL及caspase相关酶的变化。结果发现,PR能明显抑制NB4细胞增殖,并诱导细胞凋亡。随着PR浓度的增加,pml/rarα、bcl-2及survivin基因在mRNA水平表达下调,JNK、FasL、caspase3及caspase8蛋白表达增加,与PR浓度呈正相关;PR联合三氧化二砷(arsenic trioxide,ATO)处理后上述作用更为明显。结论:PR诱导NB4细胞凋亡的机制可能与JNK相关信号分子的活化有关;PR联合ATO具有协同诱导NB4细胞凋亡的作用。展开更多
JWA, a cytoskeleton associated gene, was primarily found to be regulated by all trans-retinoic acid (ATRA), 13 cis-retinoic acid (13 cis-RA) and 12-tetradecano-ylphorbol-13-acetate (TPA). Our previous data showed that...JWA, a cytoskeleton associated gene, was primarily found to be regulated by all trans-retinoic acid (ATRA), 13 cis-retinoic acid (13 cis-RA) and 12-tetradecano-ylphorbol-13-acetate (TPA). Our previous data showed that JWA might be involved in both cellular differentiation and apoptosis induced by several chemicals. In this study, we addressed the possible mechanism of JWA in the regulation of cell differentiation and apoptosis in NB4, a human acute promyelocytic leukemia cell line. CD11b/CD33 expression and cell cycle were analyzed for detecting of cell differentiation and apoptosis. Both reverse-transcription polymerase chain reaction (RT-PCR) and Western blot assays were used for understanding the expressions of JWA. The results showed that under the indicated concentrations ATRA (10-6 mol/L) and As2O3 (10-6 mol/L) induced cell differentiation and apoptosis separately; while both 4HPR (10-6mol/L) and TPA (10-7 mol/L) showed dual-directional effects on NB4 cells, they not only trigger cells’展开更多
基金This work was supported in part by the National Natural Science Foundation of China (Grant Nos. 30070664 and 30170812)the Natural Science Foundation of Jiangsu Province (Grant No. BK99133) the Science Foundation of Nanjing Medical University (Grant N
文摘JWA, a cytoskeleton associated gene, was primarily found to be regulated by all trans-retinoic acid (ATRA), 13 cis-retinoic acid (13 cis-RA) and 12-tetradecano-ylphorbol-13-acetate (TPA). Our previous data showed that JWA might be involved in both cellular differentiation and apoptosis induced by several chemicals. In this study, we addressed the possible mechanism of JWA in the regulation of cell differentiation and apoptosis in NB4, a human acute promyelocytic leukemia cell line. CD11b/CD33 expression and cell cycle were analyzed for detecting of cell differentiation and apoptosis. Both reverse-transcription polymerase chain reaction (RT-PCR) and Western blot assays were used for understanding the expressions of JWA. The results showed that under the indicated concentrations ATRA (10-6 mol/L) and As2O3 (10-6 mol/L) induced cell differentiation and apoptosis separately; while both 4HPR (10-6mol/L) and TPA (10-7 mol/L) showed dual-directional effects on NB4 cells, they not only trigger cells’
