Institute for Cancer Research in People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, P.R. China.
Int J Oncol. 2010 Jul;37(1):103-10.
Glioblastoma is a highly lethal brain tumor of the human primary nervous system tumors. Previous studies demonstrated that glioblastoma stem cells were able to initiate and reform the original cancer. In this study, we found that there were expression and activation of STAT3, a key signal transduction factor and oncoprotein, in human glioblastoma stem cells (GSCs). STAT3 plays a key role in proliferation, apoptosis and differentiation in embryonic stem cells and several cancer types. To investigate the effects of STAT3 on human GSCs, the expression and activation of STAT3 were suppressed by RNAi mediated with lentivirus. We demonstrated that siRNA of STAT3 significantly suppressed STAT3 expression and activation and resulted in inhibition of cell growth in GSCs. Knockdown of STAT3 induces apoptosis and reduces significantly expression of Bcl-2 and cyclin-D in human primary GSCs, whereas no significance was achieved in BAX and caspase-3 expression. Inhibition of STAT3 expression is associated not only with decreasing of CD133+ cell proportion and increasing of GFAP and MBP expression, but also with decrease of the capacity to initiate a tumor in human primary GSCs. Together, these studies suggest that STAT3 is an important target for human GSCs in regulation of GSCs growth, apoptosis, differentiation and tumorigenic potential.
胶质母细胞瘤是一种高度致命的人类原发性神经系统肿瘤。先前的研究表明，胶质母细胞瘤干细胞能够启动和重建原始癌症。在这项研究中，我们发现人胶质母细胞瘤干细胞（GSCs）中存在 STAT3 的表达和激活，STAT3 是一种关键的信号转导因子和癌蛋白。STAT3 在胚胎干细胞和几种癌症类型中的增殖、凋亡和分化中发挥着关键作用。为了研究 STAT3 对人 GSCs 的影响，我们通过慢病毒介导的 RNAi 抑制 STAT3 的表达和激活。我们证明，STAT3 的 siRNA 显著抑制 STAT3 的表达和激活，并导致 GSCs 中的细胞生长受到抑制。STAT3 的敲低诱导细胞凋亡，并显著降低人原发性 GSCs 中 Bcl-2 和细胞周期蛋白 D 的表达，而 BAX 和 caspase-3 的表达没有显著变化。STAT3 表达的抑制不仅与 CD133+细胞比例的降低和 GFAP 和 MBP 表达的增加有关，而且与人类原发性 GSCs 中肿瘤起始能力的降低有关。总之，这些研究表明 STAT3 是调控 GSCs 生长、凋亡、分化和致瘤潜能的人 GSCs 的重要靶点。
