Inhibition of Phosphatidylinositol 3-Kinase Causes Apoptosis in Retinoic Acid-Differentiated HL-60 Leukemia Cells
Inhibition of Phosphatidylinositol 3-Kinase Causes Apoptosis in Retinoic Acid-Differentiated HL-60 Leukemia Cells
复制标题
抑制磷脂酰肌醇 3-激酶导致视黄酸分化的 HL-60 白血病细胞凋亡
作者：
Jin Ma;Qiang Liu;Y. Zeng
磷脂酰肌醇3-激酶(PI3-K)信号转导通路可抑制肿瘤细胞的凋亡。PI-3K抑制剂Wortmannin使细胞易于凋亡。分化诱导剂也可能导致细胞凋亡。为探讨Wortmannin对分化的人急性早幼粒细胞白血病细胞存活的影响，用全反式维甲酸(ATRA)诱导HL-60细胞分化，再用Wortmannin处理HL-60细胞。结果表明，分化后的HL-60细胞发生了凋亡，而未分化的HL-60细胞则未发生凋亡。促凋亡分子Bad在这种凋亡机制中发挥了作用。因此，ATRA诱导分化的HL-60细胞存活依赖于PI3-K通路传递生存信号的能力；PI3-K抑制剂wortmannin可以诱导分化的HL-60细胞凋亡。这些结果可能预示着一种通过诱导分化和信号通路调节来治疗癌症的新方法。
Phosphatidylinositol 3-kinase (PI3-K) signaling may inhibit apoptosis in neoplastic cells. The PI-3K inhibitor wortmannin renders cells apoptosis-prone. Inducers of differentiation may also cause apoptosis. To detect the effect of wortmannin on the survival of differentiated human acute promyeloid leukemia cells, HL-60 cells were induced to differentiation with treatment of all trans-retinoic acid (ATRA) followed by treatment with wortmannin. Results showed that apoptosis occurred in cells that underwent differentiation, but not in undifferentiated HL-60 cells. The pro-apoptotic molecule, Bad, played a role in this apoptotic mechanism. Thus, the survival of differentiated HL-60 cells induced by ATRA depends on the ability of the PI3-K pathway to transduce survival signals; the PI3-K inhibitor, wortmannin, can induce apoptosis of differentiated HL-60 cells. These results may indicate a novel method for treating cancer with differentiation induction and signal pathway regulation.
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影响因子：
56.9
作者：
L. Peso;M. González‐García;C. Page;R. Herrera;G. Núñez
通讯作者：
L. Peso;M. González‐García;C. Page;R. Herrera;G. Núñez
DOI：
10.1073/pnas.94.8.3627
发表时间：
1997-04-15
影响因子：
11.1
作者：
Ahmed, NN;Grimes, HL;Tsichlis, PN
通讯作者：
Tsichlis, PN
DOI：
10.1007/bfb0102306
发表时间：
1998-01-01
期刊：
Advances in biochemical engineering/biotechnology
影响因子：
--
作者：
Bruckheimer, E M;Cho, S H;McDonnell, T J
通讯作者：
McDonnell, T J
影响因子：
56.9
作者：
YAO, RJ;COOPER, GM
通讯作者：
COOPER, GM