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[三七皂苷Ft1下调乳腺癌细胞中缺氧诱导因子-1α(HIF-1α),抑制细胞增殖,减少迁移并促进细胞凋亡]

[Notoginsenoside Ft1 down-regulates HIF-1α, inhibits cell proliferation, decreases migration and promotes apoptosis in breast cancer cells].

作者信息

Qiu Shui-ping, Li Hong-li, Shi Hai-lian, Wu Hui, Huang Fei, Zhang Bei-bei, Wu Xiao-jun, Wang Zheng-tao

出版信息

Yao Xue Xue Bao. 2016 Jul;51(7):1091-7.

PMID:29897190
Abstract

To investigate the effect of notoginsenoside Ft1 (Ft1) on proliferation, migration and apoptosis of breast cancer cells, we conducted several assays including CCK-8 assay, Ed U staining, single cell migration assay and Hoechst 33258 staining. The effect of Ft1 on expression of apoptosis related proteins, HIF-1α, PI3K/Akt/mTOR/p70S6 K and MAPK pathways was examined with Western blot. Ft1 could significantly reduce cell survival and inhibit cell proliferation in breast cancer cells in a dose-dependent manner. Ft1 also increased chromatin condensation of MDA-MB-231 cells. Furthermore, Ft1 decreased protein expression of Bcl-2 and HIF-1α and increased expression of cleaved caspase 3 in MDA-MB-231 cells after 12 h treatment. Ft1 significantly down-regulated the levels of p-Akt, p-mTOR and p-p70S6 K as well as p-ERK1/2, but up-regulated that of p-JNK. Ft1 significantly inhibited the level of p-EGFR (Tyr1068) and p-EGFR (Ser1046/1047) in MDA-MB-231 cells. Finally, Ft1 significantly inhibited the migration path length and velocity of HS578 T cells when used at the concentration without affecting cell viability. Thus, Ft1 exhibited multiple antitumor effects including inhibition of cell survival and migration, promotion of cell apoptosis in breast cancer cells. Suppression of HIF-1α via Akt/mTOR/p70S6K and MAPK pathways may be involved in the pharmacological effect of Ft1 on cell proliferation and apoptosis of breast cancer cells.

摘要

为研究三七皂苷Ft1(Ft1)对乳腺癌细胞增殖、迁移和凋亡的影响,我们进行了多项实验,包括CCK-8实验、EdU染色、单细胞迁移实验和Hoechst 33258染色。通过蛋白质免疫印迹法检测Ft1对凋亡相关蛋白、HIF-1α、PI3K/Akt/mTOR/p70S6K和MAPK信号通路表达的影响。Ft1可显著降低乳腺癌细胞的存活率,并呈剂量依赖性抑制细胞增殖。Ft1还可增加MDA-MB-231细胞的染色质凝聚。此外,处理12小时后,Ft1可降低MDA-MB-231细胞中Bcl-2和HIF-1α的蛋白表达,并增加裂解的caspase 3的表达。Ft1可显著下调p-Akt、p-mTOR和p-p70S6K以及p-ERK1/2的水平,但上调p-JNK的水平。Ft1可显著抑制MDA-MB-231细胞中p-EGFR(Tyr1068)和p-EGFR(Ser1046/1047)的水平。最后,当以不影响细胞活力的浓度使用时,Ft1可显著抑制HS578T细胞的迁移路径长度和速度。因此,Ft1具有多种抗肿瘤作用,包括抑制细胞存活和迁移、促进乳腺癌细胞凋亡。通过Akt/mTOR/p70S6K和MAPK信号通路抑制HIF-1α可能参与了Ft1对乳腺癌细胞增殖和凋亡的药理作用。

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