摘要
研究大黄素对炎症介导的结肠癌细胞转移的抑制作用。采用MTT法确定大黄素有效作用浓度。细胞划痕、Transwell、基质胶实验检测大黄素对LPS诱发的结肠癌细胞SW480的迁移、侵袭能力的影响。ELISA实验检测经药物处理后细胞培养基中炎性因子的变化;蛋白质免疫印迹检测LPS单独处理和LPS、大黄素共处理结肠癌细胞后,胞内EMT标志蛋白及炎症信号通路相关蛋白的表达变化;建立小鼠肺转移模型评价大黄素抑制LPS诱发的结肠癌转移的能力。结果发现,大黄素能有效抑制LPS诱发的结肠癌细胞SW480增殖、迁移和侵袭;大黄素与LPS共处理和LPS单独处理结肠癌细胞相比,培养基上清中炎性因子IL-1β、TNF-α、IL-6含量下降;此外,蛋白质免疫印迹结果显示大黄素与LPS共处理较LPS单独处理,EMT过程受到抑制,NF-κB、TLR4表达下调;肺转移模型实验显示大黄素能抑制LPS诱发的结肠癌细胞的肺转移。实验结果表明,大黄素通过抑制LPS诱发炎症因子的释放和炎性信号通路激活,进而抑制结肠癌细胞转移。
To investigate the inhibitory effect of emodin on inflammatory mediated metastasis of colon cancer cells. MTF assay was used to determine the effective concentration of emodin. The effect of emodin on migration and invasion of co- lon cancer cell line SW480 induced by LPS was evaluated by wound healing,Transwell, Matrigel invasion assay. The ex- pression of inflammatory cytokines in the culture supernatants was determined by enzyme-linked immunosorbent assay af- ter colon cancer cells were treated with LPS alone or combined with emodin. Intracellular EMT marker and inflammatory- related protein was detected by Western blot after LPS treated alone and cotreated with emodin on colon cancer cells. The lung metastasis mouse model was established to evaluate the inhibitory effect of emodin on the tumor metastasis induced by LPS. The results indicated that emodin could inhibit the proliferation, migration and invasion induced by LPS in SW480 colon cancer cells. In colon cancer cells cotreated with LPS and emodin, the level of inflammatory factors such as IL-1, TNFa and IL-6 was reduced and western-blot analysis revealed that EMT was suppressed and expression of NF-kB and TLR4 was down-regulated when compared with treatment with LPS alone. In vivo, emodin can inhibit lung metastasis of colon cancer induced by LPS. The results suggested that emodin suppressed the EMT process of colon cancer cells by inhibiting release of inflammatory factors induced by LPS and activation of inflammatory signaling pathways, thereby in- hibiting metastasis of colon cancer cells.
出处
《天然产物研究与开发》
CAS
CSCD
北大核心
2017年第12期2044-2049,2055,共7页
Natural Product Research and Development
关键词
大黄素
结肠癌
炎性因子
转移
emodin
colon cancer
inflammatory factors
metastasis
