Yang Zesong, Yang Chunxiu, Zhang Shunjun, Li Ying, Chen Jianbin
Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing;
Oncol Lett. 2013 Apr;5(4):1390-1394. doi: 10.3892/ol.2013.1159. Epub 2013 Jan 29.
The Notch signaling pathway has been shown to be involved in the progression of chronic myeloid leukemia (CML). The aim of this study was to investigate the effects of exogenous Notch2 overexpression on cell proliferation and possible mechanisms in the human CML cell line K562. When exogenous intracellular fragment of Notch2 (ICN2) was transfected into K562 cells with Lipofectamine™ 2000, the expression of Notch2 mRNA and protein were upregulated. Cell numbers decreased and the proliferation was inhibited significantly after transfection with ICN2. G1 phase cells increased and S phase cells decreased 48 h after transfection. Finally, the expression of Numb, Bcl-2, NF-κB and TGF-β1 was detected. It was found that the expression of NF-κB and TGF-β1 mRNA was increased, while Bcl-2 was downregulated, with Numb expression unchanged. Our study indicates that the Notch pathway is activated in K562 cells after ICN2 transfection. It inhibited the proliferation of K562 cells, likely by upregulating the expression of NF-κB and TGF-β1 mRNA and downregulating the expression of Bcl-2.
Notch信号通路已被证明与慢性髓性白血病(CML)的进展有关。本研究的目的是探讨外源性Notch2过表达对人CML细胞系K562细胞增殖的影响及其可能机制。当用Lipofectamine™ 2000将外源性Notch2细胞内片段(ICN2)转染到K562细胞中时,Notch2 mRNA和蛋白的表达上调。转染ICN2后细胞数量减少,增殖受到显著抑制。转染48小时后,G1期细胞增加,S期细胞减少。最后,检测了Numb、Bcl-2、NF-κB和TGF-β1的表达。发现NF-κB和TGF-β1 mRNA的表达增加,而Bcl-2表达下调,Numb表达无变化。我们的研究表明,ICN2转染后K562细胞中的Notch通路被激活。它可能通过上调NF-κB和TGF-β1 mRNA的表达以及下调Bcl-2的表达来抑制K562细胞的增殖。