姜黄素通过抑制HDGF/β-连环蛋白复合物在体外抑制人胶质瘤细胞的侵袭和迁移
[Curcumin suppresses invasiveness and migration of human glioma cells in vitro by inhibiting HDGF/β-catenin complex].
作者信息
Luo Qisheng, Luo Hongcheng, Fu Huangde, Huang Haineng, Huang Huadong, Luo Kunxiang, Li Chuanyu, Hu Rentong, Zheng Chuanhua, Lan Chuanliu, Tang Qianli
机构信息
College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha 410208, China.
Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, China.
出版信息
Nan Fang Yi Ke Da Xue Xue Bao. 2019 Aug 30;39(8):911-916. doi: 10.12122/j.issn.1673-4254.2019.08.06.
OBJECTIVE
To investigate the effect of curcumin on the invasion and migration of human glioma cells and explore the molecular mechanisms.
METHODS
MTT assay was used for screening the optimal curcumin concentrations. The effects of curcumin on the invasion and metastasis of human glioma cell lines U251 and LN229 were tested using Transwell assay, Boyden assay and wound-healing assays. The expression of the related proteins and their interactions were determined using Western blotting and coimmunoprecipitation assay.
RESULTS
Curcumin at the concentration of 20 μmol/L for 48 h was used as the optimal condition for subsequent cell treatment. In the two glioma cell lines, curcumin significantly suppressed the invasion and migration of the cells ( < 0.05) and lowered the expressions of hepatoma-derived growth factor (HDGF), Ncadherin, vimentin, Snail and Slug, but increased the expression of E-cadherin. Interference of HDGF in curcumin-treated glioma cells synergistically inhibited the epithelial-mesenchymal transition (EMT) signals, while overexpression of HDGF significantly reversed the inhibitory effect of curcumin on EMT; curcumin treatment could significantly reduce the binding of HDGF to β-catenin.
CONCLUSIONS
Curcumin suppresses EMT signal by reducing HDGF/β-catenin complex and thereby lowers the migration and invasion abilities of human glioma cells .
目的
研究姜黄素对人胶质瘤细胞侵袭和迁移的影响并探讨其分子机制。
方法
采用MTT法筛选姜黄素的最佳浓度。运用Transwell法、Boyden法和伤口愈合试验检测姜黄素对人胶质瘤细胞系U251和LN229侵袭和转移的影响。采用蛋白质免疫印迹法和免疫共沉淀试验测定相关蛋白的表达及其相互作用。
结果
将浓度为20 μmol/L的姜黄素作用48 h作为后续细胞处理的最佳条件。在两种胶质瘤细胞系中，姜黄素显著抑制细胞的侵袭和迁移（<0.05），降低肝癌衍生生长因子（HDGF）、N-钙黏蛋白、波形蛋白、Snail和Slug的表达，但增加E-钙黏蛋白的表达。干扰姜黄素处理的胶质瘤细胞中的HDGF可协同抑制上皮-间质转化（EMT）信号，而HDGF的过表达显著逆转姜黄素对EMT的抑制作用；姜黄素处理可显著降低HDGF与β-连环蛋白的结合。
结论
姜黄素通过减少HDGF/β-连环蛋白复合物来抑制EMT信号，从而降低人胶质瘤细胞的迁移和侵袭能力。
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