邱水平, 李鸿丽, 石海莲, 吴辉, 黄菲, 张蓓蓓, 吴晓俊, 王峥涛. 三七皂苷Ft1抑制乳腺癌细胞增殖、迁移及促进凋亡的机制研究J. 药学学报, 2016,51(7): 1091-1097. doi: 10.16438/j.0513-4870.2016-0051
引用本文: 邱水平, 李鸿丽, 石海莲, 吴辉, 黄菲, 张蓓蓓, 吴晓俊, 王峥涛. 三七皂苷Ft1抑制乳腺癌细胞增殖、迁移及促进凋亡的机制研究J. 药学学报, 2016,51(7): 1091-1097. doi: 10.16438/j.0513-4870.2016-0051
QIU Shui-ping, LI Hong-li, SHI Hai-lian, WU Hui, HUANG Fei, ZHANG Bei-bei, WU Xiao-jun, WANG Zheng-tao. Notoginsenoside Ft1 down-regulates HIF-1α, inhibits cell proliferation, decreases migration and promotes apoptosis in breast cancer cellsJ. Acta Pharmaceutica Sinica, 2016,51(7): 1091-1097. doi: 10.16438/j.0513-4870.2016-0051
Citation: QIU Shui-ping, LI Hong-li, SHI Hai-lian, WU Hui, HUANG Fei, ZHANG Bei-bei, WU Xiao-jun, WANG Zheng-tao. Notoginsenoside Ft1 down-regulates HIF-1α, inhibits cell proliferation, decreases migration and promotes apoptosis in breast cancer cellsJ. Acta Pharmaceutica Sinica, 2016,51(7): 1091-1097. doi: 10.16438/j.0513-4870.2016-0051

三七皂苷Ft1抑制乳腺癌细胞增殖、迁移及促进凋亡的机制研究

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

  • 摘要: 研究三七皂苷Ft1抑制乳腺癌细胞增殖、迁移,促凋亡的作用及分子机制。CCK-8法、EdU染色、Hoechst 33258染色和单细胞迁移实验分别检测细胞活力、增殖、凋亡和迁移能力;Western blot检测凋亡相关蛋白、HIF-1α、PI3K/Akt/mTOR/p70S6K和MAPK通路蛋白表达。结果表明,Ft1能降低乳腺癌细胞MDA-MB-231和MCF-7的活力,抑制MDA-MB-231和BT-549细胞的增殖。Ft1也可诱导MDA-MB-231细胞核DNA高度聚集,并且在作用12 h后,下调HIF-1α和Bcl-2,上调cleaved caspase 3蛋白表达。进一步研究发现,Ft1在降低HIF-1α蛋白表达的同时,显著减少p-Akt、p-mTOR、p-p70S6K及p-ERK1/2的蛋白表达,但增加p-JNK蛋白水平。Ft1能够显著抑制EGFR的Tyr1068和Ser1046/1047两个位点的磷酸化。在不影响HS578T细胞活力的浓度下,Ft1能够显著抑制其迁移路径长度和速度。因此,Ft1具有抑制乳腺癌细胞增殖、迁移和促进凋亡作用,其作用可能与其调控Akt/mTOR/p70S6K和MAPK通路,下调HIF-1α,抑制Bcl-2和上调cleaved caspase 3蛋白有关。

     

    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, EdU staining, single cell migration assay and Hoechst 33258 staining. The effect of Ft1 on expression of apoptosis related proteins, HIF-1α, PI3K/Akt/mTOR/p70S6K 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-p70S6K 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 HS578T 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.

     

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