Effects of Zeng Sheng Ping/ACAPHA on malignant brain tumor growth and Notch signaling.
Effects of Zeng Sheng Ping/ACAPHA on malignant brain tumor growth and Notch signaling.
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DOI：
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发表时间：
2012-07
影响因子：
2
通讯作者：
K. J. Lim;K. Rajan;C. Eberhart
中科院分区：
文献类型：
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作者：
K. J. Lim;K. Rajan;C. Eberhart
背景/目的增生平是一种传统的中药制剂，用于预防肿瘤的进展和生长。它已被证明可以抑制Notch 2在小鼠肺癌模型中的表达，从而使我们研究其在Notch依赖性脑肿瘤中的治疗潜力。材料和方法在神经胶质瘤和髓母细胞瘤细胞系中进行3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑（MTS）、凋亡和定量实时聚合酶链反应（RT-PCR）分析，并在DAOY侧腹异种移植物中进行形态学分析。结果ZSP在体外抑制脑肿瘤生长，部分通过诱导细胞凋亡。还观察到Notch 2受体、途径靶点Hairy/分裂增强子同源物1（Hes 1）以及干细胞标志物巢蛋白和CD 133的下调。在口服ZSP治疗的小鼠中，也观察到肿瘤质量的减少和DAOY异种移植物的坏死部分的增加，但这些并不显著。结论ZSP在体外可抑制脑肿瘤的生长及Notch通路成员和干细胞标志物的表达。
BACKGROUND/AIM Zeng Sheng Ping (ZSP) is a traditional herbal remedy used to prevent progression and growth of neoplastic lesions. It has been shown to inhibit Notch2 expression in a murine lung cancer model, leading us to investigate its therapeutic potential in Notch-dependent brain tumors. MATERIALS AND METHODS 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), apoptosis, and quantitative real-time polymerase chain reaction (RT-PCR) analyses were performed in glioma and medulloblastoma cell lines, and morphological analyses in DAOY flank xenografts. RESULTS ZSP inhibited brain tumor growth in vitro, in part, by apoptotic induction. Down-regulation of the Notch2 receptor, the pathway target Hairy/Enhancer of Split homolog 1 (Hes1), and of the stem cell markers Nestin and CD133 was also observed. Reductions in tumor mass and increases in the necrotic fraction of DAOY xenografts, in mice treated with oral ZSP were also observed, but these were not significant. CONCLUSION ZSP can block brain tumor growth and the expression of Notch pathway members and stem cell markers in vitro.