| 陈奥,甘琪,戚欣,等.多硫代二酮哌嗪类化合物1004体外对MDA-MB-231细胞转移能力的影响及机制研究[J].中国海洋药物,2019,38(4):11-18. |
| 多硫代二酮哌嗪类化合物1004体外对MDA-MB-231细胞转移能力的影响及机制研究 |
| Effect of epipolythiodiketopiperazine 1004 on the metastatic-ability of MDA-MB-231 cells in vitro and related mechanism study |
| 投稿时间：2018-12-17 修订日期：2019-03-20 |
| DOI： |
| 中文关键词: MDA-MB-231 转移 信号通路 AKT ERK |
| English Keywords:MDA-MB-231 Metastasis Signaling pathway AKT ERK |
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| 中文摘要: |
| 摘要：目的 检测多硫代二酮哌嗪类化合物1004体外对三阴性乳腺癌MDA-MB-231细胞转移能力的影响，并初步研究其作用机制。方法 利用磺酰罗丹明染色法（SRB）检测1004作用于MDA-MB-231细胞24和72 h的细胞毒活性；细胞粘附实验检测1004对MDA-MB-231细胞外基质粘附的影响；划痕实验和Transwell侵袭实验，分别检测1004对MDA-MB-231细胞迁移和侵袭的影响；明胶酶谱法检测1004对MDA-MB-231细胞基质金属蛋白酶MMP9活性的影响；Western Blot检测1004对MDA-MB-231细胞N-cadherin、Snail、c-Myc和FGFR1的蛋白表达的影响，检测AKT和ERK表达和活化水平。结果 1004作用于MDA-MB-231细胞72 h的IC50为（6.28±1.25）μmol?L-1，而1004作用于MDA-MB-231细胞24 h的IC50超过100 μmol?L-1。1004作用于MDA-MB-231细胞可增加细胞粘附，并抑制细胞的迁移和侵袭。1004可以显著降低N-cadherin、c-Myc 及Snail 的表达水平，并抑制MMP9 的活性。1004 作用于MDA-MB-231细胞可以浓度依赖性地引起FGFR1的表达下调，并抑制下游ERK和AKT 的活化。结论 1004体外对MDA-MB-231细胞具有转移抑制活性，其机制可能与下调FGFR1的蛋白水平并抑制FGFR信号通路有关。 |
| English Summary: |
| Abstract: Objective To investigate the effect of epipolythiodiketopiperazine (ETP) 1004 on the metastatic ability of MDA-MB-231 cells in vitro and its related mechanism. Methods The cytotoxic activities of 1004 on MDA-MB-231 cells at 24 h and 72 h were detected by sulforhodamine staining (SRB). The effect of 1004 on the adhesion of MDA-MB-231 cells was detected by cell adhesion assay. Wound healing assay and transwell invasion assay were used to detect the effects of 1004 on MDA-MB-231 cell migration and invasion; Zymography was used to detect the effect of 1004 on MDA-MB-231 cell matrix metalloproteinase MMP9 activity; Western Blot assay was used to detect the effects of 1004 on protein expressions of N-cadherin, Snail, c-Myc and FGFR1 in MDA-MB-231 cells, expression and activation levels of AKT and ERK. Results The IC50 of 1004 on MDA-MB-231 cells was（6.28±1.25）μmol?L-1 for 72 h, while the IC50 of 1004 on MDA-MB-231 cells for 24 h was over 100 μmol?L-1, 1004 increased the adhesion and inhibited migration and invasion of MDA-MB-231. 1004 significantly reduced the expression levels of N-cadherin, c-myc and snail, and inhibited the activity of MMP9. Furthermore, the mechanism study showed that the level of FGFR1 was down-regulated in a concentration-dependent manner accompanied by inactivation of ERK and AKT after 1004 treatment. Conclusion 1004 exhibits metastasis inhibitory activity on MDA-MB-231 cells in vitro, which may be related to down-regulation of FGFR1 signaling pathway. |
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