Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: involvement of the β-catenin pathway
Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: involvement of the β-catenin pathway
复制标题
Cleistanthin A 抑制 MDA-MB-231 人乳腺癌细胞的侵袭：β-连环蛋白途径的参与
DOI：
10.1007/s43440-019-00012-1
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发表时间：
2020-02-01
影响因子：
4.4
通讯作者：
Zhu, Li
中科院分区：
文献类型：
--
作者：
Liu, Siyuan;Wang, Lu;Zhu, Li
背景资料：白藜芦醇甲（CleA）是一种天然的二叶素糖苷，已被证明可以抑制癌细胞的侵袭，但其潜在的机制尚不清楚。本研究旨在探讨CleA对人乳腺癌MDA-MB-231细胞侵袭能力的抑制作用及其机制。采用创伤愈合实验和transwell实验检测MDA-MB-231细胞的迁移和侵袭能力。明胶酶谱法检测基质金属蛋白酶（MMPs）活性。通过qRT-PCR和Western blotting分别检测mRNA和蛋白水平。结果：CleA能有效抑制MDA-MB-231细胞的迁移和侵袭，抑制MMP-2/9的表达和活化。此外，CleA处理降低了β-连环蛋白的表达和核转位，以及Cyclin D1和c-myc基因的转录。此外，CleA对β-连环蛋白途径的抑制作用归因于通过抑制GSK 3 β磷酸化促进β-连环蛋白降解。结论：CleA抑制MDA-MB-231细胞的侵袭能力，可能是通过β-catenin途径实现的。
Background: Cleistanthin A (CleA), a natural diphyllin glycoside, has been shown to suppress the invasion of cancer cells, but the underlying mechanisms remain unclear. Here, the inhibitory effect of CleA on the invasion of MDA-MB-231 human breast cancer cells was investigated, and the mechanisms involved were clarified.Methods: Cell viability was studied by MTT assay. The migration and invasion of MDA-MB-231 cells were assessed by wound healing assay and transwell assay, respectively. The enzymatic activity of matrix metalloproteinases (MMPs) was detected by gelatin zymography. mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. Nuclear translocation of beta-catenin was observed by immunofluorescence and detected by Western blotting.Results: CleA effectively inhibited the migration and invasion of MDA-MB-231 cells and suppressed the expression and activation of MMP-2/9. Moreover, the expression and nuclear translocation of beta-catenin were reduced by CleA treatment, as well as transcription of the Cyclin D1 and c-myc genes. In addition, the inhibitory effect of CleA on the beta-catenin pathway was attributed to the promotion of beta-catenin degradation by inhibition of GSK3 beta phosphorylation. When the phosphorylation of GSK3 beta was induced by LiCl, the inhibitory effect of CleA on the beta-catenin pathway and the invasion of MDA-MB-231 cells were almost reversed.Conclusion: CleA suppressed the invasion of MDA-MB-231 cells, likely through the beta-catenin pathway.