Zhang Bing, Xia Chun
Medical School, Xiamen University, Xiamen, Fujian Province, 361005, PR China.
Cell Mol Biol Lett. 2009;14(3):466-80. doi: 10.2478/s11658-009-0013-5. Epub 2009 Feb 23.
Protein kinase B (PKB/Akt) is a serine-threonine kinase functioning downstream of phosphatidylinositol 3-kinase (PI-3 kinase) in response to mitogen or growth factor stimulation. In several cell types, it plays an important anti-apoptotic role. TPA is a potent regulator of the growth of many different cell types. Here, we detected that TPA could induce cell apoptosis in the gastric cancer cell line, BGC-823. We also found that TPA inhibited the expression of PKB/Akt in a TPA concentration- and time-dependent manner. Furthermore, TPA inhibited the phosphorylation of PKB at Ser473, but did not affect the phosphorylation of Thr308. It only attenuated the expression of PKB/Akt and the phosphorylation of Ser473 in the cell nucleus, whereas it did not change the PKB/Akt distribution in BGC-823 cells. These results suggest that PKB/Akt inhibition by TPA may be the important factor in the mechanism of effect of TPA on gastric cell lines.
蛋白激酶B(PKB/Akt)是一种丝氨酸 - 苏氨酸激酶,在有丝分裂原或生长因子刺激下,于磷脂酰肌醇3激酶(PI - 3激酶)下游发挥作用。在几种细胞类型中,它发挥着重要的抗凋亡作用。佛波酯(TPA)是多种不同细胞类型生长的有效调节剂。在此,我们检测到TPA可诱导胃癌细胞系BGC - 823发生细胞凋亡。我们还发现TPA以TPA浓度和时间依赖性方式抑制PKB/Akt的表达。此外,TPA抑制PKB在Ser473位点的磷酸化,但不影响Thr308位点的磷酸化。它仅减弱细胞核中PKB/Akt的表达和Ser473位点的磷酸化,而不改变BGC - 823细胞中PKB/Akt的分布。这些结果表明,TPA对PKB/Akt的抑制作用可能是TPA对胃细胞系作用机制中的重要因素。