Delayed growth of glioma by a polysaccharide from Aster tataricus involve upregulation of Bax/Bcl-2 ratio, activation of caspase-3/8/9, and downregulation of the Akt

Delayed growth of glioma by a polysaccharide from Aster tataricus involve upregulation of Bax/Bcl-2 ratio, activation of caspase-3/8/9, and downregulation of the Akt
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DOI:
10.1007/s13277-013-1243-8
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发表时间:
2014-03-01
期刊:
影响因子:
--
通讯作者:
Xing, Yi-Qiao
Xing, Yi-Qiao
中科院分区:
其他
文献类型:
--
作者:
Du, Lei;Mei, Hai-Feng;Xing, Yi-Qiao

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本研究采用DEAE-SepharoseCL-6 B离子交换层析和SepharoseCL-6 B凝胶过滤层析从紫菀中分离纯化了一种均一的多糖(ATP-Ⅱ),其分子量为3.4 × 10 ~(4)Da。单糖组分分析表明,ATP-II由葡萄糖、半乳糖、甘露糖、鼠李糖和阿拉伯糖组成,摩尔比为2.1:5.2:2.1:1.0:1.2。我们评估了ATP-Ⅱ在体外和体内对胶质瘤C6细胞的抗癌效果和相关机制。结果表明,ATP-Ⅱ处理C6细胞后,细胞增殖受到抑制,这种生物学效应是通过诱导DAN损伤,进而诱导细胞凋亡实现的。同样地,口服ATP-II给药导致胶质瘤肿瘤的一致消退,并通过增加Bax/Bcl-2的比率和caspase-3、caspase-8和caspase-9级联的活化来诱导移植肿瘤组织的凋亡。重要的是,在肿瘤组织中成功检测到的Akt的有效下调是ATP-II延缓肿瘤生长的独特贡献。这些数据表明,ATP-Ⅱ可能是一个潜在的候选人胶质瘤治疗。
In this study, a homogeneous polysaccharide (ATP-II), with a molecular weight of 3.4 x 10(4) Da, was successfully purified from Aster tataricus by DEAE-Sepharose CL-6B ion exchange and Sepharose CL-6B gel filtration chromatography. Monosaccharide component analysis indicated that ATP-II was composed of glucose, galactose, mannose, rhamnose, and arabinose in molar ratios of 2.1:5.2:2.1:1.0:1.2. We evaluated the anticancer efficacy and associated mechanisms of ATP-II on glioma C6 cells in vitro and in vivo. The results showed that treatment of C6 cells with ATP-II inhibited cell proliferation and this biological response came from induction of DAN damage and consequent inducing apoptosis. Likewise, oral ATP-II administration resulted in consistent regression of glioma tumors and induced apoptosis of transplanted tumor tissues by increasing the ratio of Bax/Bcl-2 and activation of caspase-3, caspase-8, and caspase-9 cascade. Importantly, the efficient downregulation of Akt, which is successfully detected in tumor tissues, is a unique contribution to retard the tumor growth by ATP-II. These data suggest that ATP-II may be a potential candidate for glioma treatment.