Anti-tumor effect of polysaccharides from Scutellaria barbata D. Don on the 95-D xenograft model via inhibition of the C-met pathway.
Anti-tumor effect of polysaccharides from Scutellaria barbata D. Don on the 95-D xenograft model via inhibition of the C-met pathway.
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DOI：
10.1254/jphs.13276fp
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发表时间：
2014-07
影响因子：
3.5
通讯作者：
Xiaokun Yang;Ya-dong Yang;Shuqian Tang;Hui Tang;Gui-hong Yang;Qiaoyu Xu;Jin-jin Wu
中科院分区：
文献类型：
--
作者：
Xiaokun Yang;Ya-dong Yang;Shuqian Tang;Hui Tang;Gui-hong Yang;Qiaoyu Xu;Jin-jin Wu
从半枝莲中分离的多糖（PSB）已被报道具有抗肿瘤作用。为了研究潜在的机制，使用高度侵袭性、转移性和磷酸-c-Met过表达的肺癌细胞95-D细胞系。结果表明，PSB在体外不仅能抑制95-D细胞的增殖（IC（50）= 35.2 μg/mL），而且能下调磷酸化c-Met及其下游信号分子磷酸化Erk和磷酸化Akt的表达。在体内，PSB以剂量依赖性方式抑制95-D皮下异种移植模型中的肿瘤生长;在每天一次腹腔注射3周后，100和200 mg/kg处理的肿瘤生长抑制T/C比率分别为42.72%和13.6%。在体内研究结束时，收获肿瘤组织用于进一步评估c-Met、AKT和ERK的磷酸化水平。体外实验结果表明，PSB对c-Met及其下游信号分子的磷酸化也有明显的抑制作用。免疫组化分析显示肿瘤细胞增殖（Ki 67）和微血管密度（CD 31）的降低呈剂量依赖性抑制。综上所述，PSB通过直接调控c-Met信号通路对人肺癌95-D的体内外生长具有抑制作用，其抗肿瘤作用主要是基于其抗增殖和抗血管生成作用。
Polysaccharides isolated from Scutellaria barbata (PSB) have been reported to have anti-tumor effects. To investigate the underlying mechanism, a highly invasive, metastatic and phospho-c-Met overexpression lung carcinoma cell, 95-D cell line was used. The results showed that in vitro, PSB not only could inhibit the proliferation of 95-D cell line (IC(50) = 35.2 μg/mL), but also down-regulated the expression of phospho-c-Met and its downstream signaling molecules including phospho-Erk and phospho-Akt. In vivo, PSB inhibited tumor growth in the 95-D subcutaneous xenograft model in a dose-dependent manner; after once-daily intraperitoneal injection for 3 weeks, tumor growth inhibition T/C ratio for 100 and 200 mg/kg treatments was 42.72% and 13.6%, respectively. In the end of the in vivo study, tumor tissues were harvested for further evaluation of the phosphorylation level of c-Met, AKT, and ERK. Ex vivo results demonstrated that the phosphorylation of c-Met and its downstream signaling molecules were also significantly inhibited by PSB. Immunohistochemistry analysis showed dose-dependent inhibition of tumor cell proliferation (Ki67) and reduction of microvessel density (CD31). In summary, the results indicated that PSB exerted anti-tumor growth activity on human lung cancer 95-D in vitro and in vivo by directly regulating the c-Met signaling pathway and the anti-tumor effects were mainly based on its anti-proliferation and anti-angiogenesis action.