Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways.
Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways.
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DOI：
10.1016/j.gene.2016.07.012
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发表时间：
2016-10
期刊：
影响因子：
3.5
通讯作者：
Xinge Zhao;Xin Li;Qianyao Ren;Jing Tian;Jian Chen
中科院分区：
文献类型：
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作者：
Xinge Zhao;Xin Li;Qianyao Ren;Jing Tian;Jian Chen
毛蕊异黄酮（Calycosin）是从中药丹参中提取的主要成分，在多种肿瘤细胞系中具有抑制细胞增殖和诱导细胞凋亡的作用，但其作用机制尚不清楚。在本研究中，我们的目的是确定毛蕊异黄酮对大肠癌细胞体外和体内增殖的潜在影响，并阐明其潜在的分子作用机制。用不同浓度的毛蕊异黄酮或ER β抑制剂PHTPP处理结肠癌细胞系SW 480和LoVo以及宫颈癌细胞系HeLa。采用CCK-8法、流式细胞术和Hoechst 33258染色法评价对细胞增殖和凋亡的影响。实时定量PCR检测ERβ和miR-95的mRNA水平。Western blot分析ERβ、ERα、IGF-1 R和p-Akt蛋白表达水平。我们证明毛蕊异黄酮抑制SW 480和LoVo细胞的增殖，并诱导凋亡，特别是在SW 480细胞中，但不在HeLa细胞中。毛蕊异黄酮可增加SW 480细胞中ERβ的表达，降低ERα、IGF-1 R和p-Akt的表达，同时下调miR-95。抑制ERβ可阻断miR-95的变化，从而抑制SW 480细胞凋亡。此外，毛蕊异黄酮显著抑制裸鼠中的异种移植肿瘤生长。结论：毛蕊异黄酮通过调节IGF-1 R、PI 3 K/Akt信号通路和miR-95表达，抑制结直肠癌细胞的增殖。
Calycosin, the main component extractable from the herb Radix astragali, has been shown to inhibit cellular proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanisms by the way in which this occurs remain unclear. In the present study, we aimed to determine the potential effects of calycosin on proliferation in colorectal cancer cellsin vitroandin vivoand to elucidate the underlying molecular mechanisms of action. Colorectal cancer cell lines SW480 and LoVo and cervical cancer cell line HeLa were treated with various concentrations of calycosin or plus ER beta (ERβ) inhibitor PHTPP. The CCK8 assay, flow cytometry, and Hoechst 33258 stain were used to assess the effects on cellular proliferation and apoptosis. The mRNA levels of ERβ and miR-95 were quantified by real-time PCR. The protein expression levels of ERβ, ERα, IGF-1R, and p-Akt were evaluated by Western blot analysis. We demonstrated that calycosin inhibited the proliferation in SW480 and LoVo cells and induced apoptosis, particularly in SW480 cells, but not in HeLa cells. Calycosin increased ERβ expression and reduced the ERα, IGF-1R, and p-Akt expression alongside down-regulation of miR-95 in SW480 cells. Inhibiting ERβ blocked the change of miR-95 and the resulting increase in apoptosis in SW480 cells. Additionally, calycosin significantly suppressed xenograft tumor growth in nude mice. In conclusion, calycosin exerts an inhibitory effect on proliferation of CRC cellsin vivoandin vitro, through ERβ-mediated regulation of the IGF-1R, PI3K/Akt signaling pathways and of miR-95 expression.