Kim Su-Ryun, Bae Moon-Kyoung, Kim Jee-Young, Wee Hee-Jun, Yoo Mie-Ae, Bae Soo-Kyung
Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 602-739, South Korea.
Biochem Biophys Res Commun. 2009 Sep 18;387(2):342-7. doi: 10.1016/j.bbrc.2009.07.022. Epub 2009 Jul 10.
Aspirin has been reported to induce apoptosis in various cancer cell lines. However, the apoptotic effects of aspirin on human brain tumor cells are not well understood. Here, we have assessed the effect of aspirin on human gliobalstoma cell line A172 and found that aspirin induced the apoptosis of A172 cells, as determined by TUNEL assay, FACS analysis, and Hoechst staining. The underlying mechanism of this effect consists of reduction in the level of phosphorylated STAT3 (Tyr705), a transcription factor required for survival of A172 cells. Moreover, the expression of STAT3 target genes such as Cyclin D1, XIAP, and Bcl-2 that are essential for cell growth and survival was apparently attenuated after aspirin treatment. We also showed that the expression and secretion of interleukin-6 (IL-6), leading to STAT3 phosphorylation, was inhibited by aspirin. When administered exogenous IL-6 to aspirin-treated A172 cells, the phosphorylation of STAT3 and cellular apoptosis were restrained compared to aspirin only-treated cells. Taken together, our results indicate that aspirin causes apoptosis via down-regulation of IL-6-dependent STAT3 signaling, suggesting that aspirin could be therapeutically useful for a potential anti-glioblastoma therapeutic approach.
据报道，阿司匹林可诱导多种癌细胞系发生凋亡。然而，阿司匹林对人脑肿瘤细胞的凋亡作用尚未完全明确。在此，我们评估了阿司匹林对人胶质母细胞瘤细胞系A172的影响，发现通过TUNEL检测、流式细胞术分析和Hoechst染色确定，阿司匹林可诱导A172细胞凋亡。这种作用的潜在机制包括磷酸化STAT3（Tyr705）水平降低，STAT3是A172细胞存活所需的一种转录因子。此外，阿司匹林处理后，对细胞生长和存活至关重要的STAT3靶基因如细胞周期蛋白D1、XIAP和Bcl-2的表达明显减弱。我们还表明，阿司匹林可抑制导致STAT3磷酸化的白细胞介素-6（IL-6）的表达和分泌。当向经阿司匹林处理的A172细胞中加入外源性IL-6时，与仅用阿司匹林处理的细胞相比，STAT3的磷酸化和细胞凋亡受到抑制。综上所述，我们的结果表明阿司匹林通过下调IL-6依赖性STAT3信号通路导致细胞凋亡，提示阿司匹林可能对潜在的抗胶质母细胞瘤治疗方法具有治疗作用。
