异鼠李素对乳腺癌细胞的作用机制
Mechanism of isorhamnetin on breast cancer cells
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摘要: 为探讨异鼠李素对乳腺癌细胞中的作用及其机制，以两种乳腺癌细胞株MCF7和BT549作为模型细胞株，通过加入不同浓度的异鼠李素，采用MTT法检测其对细胞增殖活性的抑制作用。在确定增殖抑制作用的基础上，采用流式细胞术测定异鼠李素对细胞周期和凋亡的影响，及采用免疫印迹的方法观察异鼠李素对细胞增殖及凋亡信号通路的影响。实验结果显示，异鼠李素可显著抑制乳腺癌细胞株MCF7及BT-549的增殖，其IC50分别为11.72和8.74 μmol/L；通过流式细胞术检测，发现异鼠李素可引起细胞G1期的周期阻滞及促进细胞的凋亡，信号通路分析显示异鼠李素可减少细胞增殖通路蛋白AKT和ERK的磷酸化及增殖核抗原Ki67的表达，减少Bcl-2的表达及增加Bax的表达，促进Caspase 3的剪切，从而导致细胞的凋亡。因此，异鼠李素具有显著的抗乳腺癌作用，其作用机制与抑制细胞的增殖通路及促进细胞的凋亡有关。Abstract: This aim of this study is to explore the effect of isorhamnetin on the cell proliferation of breast cancer cells. Two breast cancer cell lines MCF7 and BT549 treated with different concentrations of isorhamnetin were examined for cell proliferation by using MTT assay. The effect of isorhamnetin on cell cycle and apoptosis was determined by flowcytometry. The effect of isorhamnetin on cell proliferation and apoptosis signaling pathway was examined by Western blot analysis. The results showed isorhamnetin can significantly inhibited the proliferation of breast cancer cell lines MCF7 and BT-549, and its IC50 was 11. 72 μmol/L and 8. 74 μmol/L, respectively. Isorhamnetin treatment resulted in cell cycle arrest at G1 phase and promote apoptosis. Consistent with this finding, isorhamnetin treatment significantly inhibited the AKT and ERK phosphorylation and the expression of proliferating nuclear antigen Ki67. Furthermore, isorhamnetin resulted in the decreased expression of Bcl-2 with concomitant decrease of Bcl-2 expression, subsequently causing the increase of cleaved Caspase-3 and cell apopotosis. Thus, isorhamnetin can significantly inhibit breast cancer cells by both inhibiting cell proliferation and promoting apoptosis.
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Keywords:
- isorhamnetin /
- breast cancer /
- proliferation /
- apoptosis /
- mechanism
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