School of Life Sciences, Shanghai University, No. 99, Shangda Road, Shanghai 200444, China.
J Clin Neurosci. 2012 Mar;19(3):443-6. doi: 10.1016/j.jocn.2011.04.017. Epub 2012 Jan 18.
Malignant gliomas are highly invasive tumours associated with high levels of mortality, and the treatment of gliomas remains a major neurosurgical challenge. Stat3, a member of the signal transducer and activator of transcription family, has a critical role in a variety of cancer cells. We have previously shown that downregulation of Stat3 decreases invasiveness and induces apoptosis in U251 human glioma cells in vitro, but to date it has been unclear whether this treatment would be beneficial in vivo. In the present study, we found that downregulation of Stat3 via RNAi suppressed tumour growth in a xenograft mouse model by inducing apoptosis of U251 tumour cells and inhibiting tumour neo-angiogenesis. We also found that Stat3 RNAi suppresses the expression of Bcl-2 in vivo to induce apoptosis. These results indicate that Stat3 is a critical factor in the survival of patients with glioma, and that targeting Stat3 may offer a potential therapeutic approach.
恶性脑胶质瘤是一种高度侵袭性肿瘤,死亡率高,胶质瘤的治疗仍然是神经外科的一大挑战。Stat3 是信号转导和转录激活因子家族的成员,在多种癌细胞中发挥关键作用。我们之前已经表明,Stat3 的下调可降低 U251 人胶质瘤细胞的侵袭性并诱导其凋亡,但迄今为止,尚不清楚这种治疗方法在体内是否有益。在本研究中,我们发现通过 RNAi 下调 Stat3 通过诱导 U251 肿瘤细胞凋亡和抑制肿瘤新生血管生成来抑制异种移植小鼠模型中的肿瘤生长。我们还发现 Stat3 RNAi 抑制体内 Bcl-2 的表达诱导细胞凋亡。这些结果表明 Stat3 是脑胶质瘤患者生存的关键因素,靶向 Stat3 可能提供一种潜在的治疗方法。