Triple negative breast cancer (TNBC) is the most severe type of breast cancer due to the lack of specific targets and rapid metastasis, which result in the poor prognosis. Recently, phosphatidylinositol 3-kinase (PI3K)/Akt pathway has emerged as a potential target for the treatment of TNBC. In our research interest to discover phytochemicals targeting TNBC, we have investigated wikstromol from Wikstroemia indica using the human TNBC MDA-MB-231 cells. The results showed wikstromol at 10 μM inhibited cell growth of MDA-MB-231 cells which was confirmed by MTT assay. Further DAPI staining has revealed wikstromol at 10 μM induced apoptosis of cancer cells, which was associated with the activation of caspase-3 following down-regulation of Bcl-2 as well as up-regulation of Bax, cleaved PARP and phosphorylated p53. Meanwhile, it was observed at 0.1 μM wikstromol suppressed the migration of the cancer cells via decreasing transcription of NF-κB and reducing activity and secretion of downstream MMP-9. In addition, p-PI3K and p-Akt were down-regulated in MDA-MB-231 cells in the presence of wikstromol at 0.1 μM, which indicated inactivation of PI3K/Akt pathway was involved in these inhibitory effects.

中文翻译：

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来自印度Wikstroemia的Wikstromol通过抑制PI3K / Akt途径诱导凋亡并抑制MDA-MB-231细胞的迁移。

三阴性乳腺癌（TNBC）是最严重的乳腺癌类型，原因是缺乏特异性靶标和转移迅速，导致预后不良。最近，磷脂酰肌醇3-激酶（PI3K）/ Akt途径已成为治疗TNBC的潜在靶标。为了发现针对TNBC的植物化学物质，我们进行了研究，使用人类TNBC MDA-MB-231细胞研究了来自Wikstroemia indica的wikstromol。结果显示10μM的维克甾醇抑制了MDA-MB-231细胞的细胞生长，这已通过MTT分析证实。进一步的DAPI染色显示wikstromol以10μM诱导的癌细胞凋亡，与bcl-2的下调以及Bax的上调，PARP的裂解和磷酸化的p53上调后caspase-3的激活有关。同时，观察到为0。1μMwikstromol通过减少NF-κB的转录并减少下游MMP-9的活性和分泌来抑制癌细胞的迁移。另外，在存在0.1μMwikstromol的情况下，MDA-MB-231细胞中的p-PI3K和p-Akt被下调，表明PI3K / Akt途径的失活与这些抑制作用有关。