西伯利亚玉竹多糖通过 TLR4-MAPK/NF-κB 信号通路发挥抗癌作用。
Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4-MAPK/NF-κB signaling pathways.
机构信息
Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
The Second Clinic College, Chongqing Medical University, Chongqing 400016, China.
出版信息
Int J Biol Macromol. 2018 May;111:813-821. doi: 10.1016/j.ijbiomac.2018.01.070. Epub 2018 Jan 16.
OBJECTIVE
To investigate the anti-cancer effect of Polygonatum sibiricum polysaccharides (PSP) and the underlying mechanism.
METHODS
Tumor-bearing mice were randomly divided into normal saline (NS) group, adriamycin (ADM) group, PSP group and lipopolysaccharide (LPS) group. RAW264.7 cells were pre-treated with or without TLR4 inhibitor or MyD88 inhibitor. Quantitative RT-PCR and Western blot were performed to detect the mRNA and protein expressions, respectively. ELISA and Griess reaction was used to measure cytokines and NO levels. Flow cytometry was employed to examine T-lymphocyte subset and CCK-8 assay was used for cell viability.
RESULTS
The in vivo experiment found that PSP inhibited tumor growth and improved the spleen index, thymus index, the cytokines secretion and CD4/CD8 lymphocytes ratio. Compared with the NS group, the mRNA and protein expressions of the critical nodes inTLR4-MAPK/NF-κB signaling pathways (except TRAM) significantly increased in PSP group, as well as the NO and cytokines levels. Nevertheless, PSP had no obvious effects on TRAM. Further analysis showed that PSP effects on the critical nodes in TLR4-MAPK/NF-κB signaling pathways were suppressed by inhibitor in vitro.
CONCLUSION
The immunoenhancement effect of PSP against lung cancer is mediated by TLR4-MAPK/NF-κB signaling pathways.
目的
研究玉竹多糖（PSP）的抗癌作用及其作用机制。
方法
荷瘤小鼠随机分为生理盐水（NS）组、阿霉素（ADM）组、PSP 组和脂多糖（LPS）组。RAW264.7 细胞预先用 TLR4 抑制剂或 MyD88 抑制剂处理。分别采用定量 RT-PCR 和 Western blot 检测 mRNA 和蛋白表达。采用 ELISA 和 Griess 反应检测细胞因子和 NO 水平。采用流式细胞术检测 T 淋巴细胞亚群，采用 CCK-8 法检测细胞活力。
结果
体内实验发现 PSP 抑制肿瘤生长，提高脾指数、胸腺指数、细胞因子分泌和 CD4/CD8 淋巴细胞比值。与 NS 组相比，PSP 组 TLR4-MAPK/NF-κB 信号通路关键节点（TRAM 除外）的 mRNA 和蛋白表达明显增加，NO 和细胞因子水平也明显增加。然而，PSP 对 TRAM 没有明显影响。进一步分析表明，PSP 对 TLR4-MAPK/NF-κB 信号通路关键节点的作用在体外被抑制剂所抑制。
结论
PSP 对肺癌的免疫增强作用是通过 TLR4-MAPK/NF-κB 信号通路介导的。
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