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肖玉洁,黄立中,龚辉,戴新军,朱旭,冯磊,王婷.黄芩苷对缺氧三阴性乳腺癌干细胞增殖及HIF-1α、IGF-Ⅱ、L-selectin的影响[J].湖南中医药大学学报英文版,2022,42(11):1870-1875.[Click to copy
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This paper
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黄芩苷对缺氧三阴性乳腺癌干细胞增殖及HIF-1α、IGF-Ⅱ、L-selectin的影响 |
肖玉洁,黄立中,龚辉,戴新军,朱旭,冯磊,王婷 |
(湖南中医药大学, 湖南 长沙 410208;湖南省中医药研究院附属医院, 湖南 长沙 410006;株洲市中心医院, 湖南 株洲 412007) |
摘要: |
目的 研究黄芩苷对缺氧乳腺癌干细胞MDA-MB-231增殖及低氧诱导因子-1α(hypoxia inducible factor-1, HIF-1α)、胰岛素样生长因子-Ⅱ(insulin-like growth factor, IGF-Ⅱ)、L-选择素(L-selectin)的影响。方法 四甲基偶氮唑蓝法检测不同浓度(12.5、25.0、50.0、100.0、200.0 mg/L)黄芩苷对缺氧乳腺癌干细胞MDA-MB-231的细胞生长抑制率的影响,筛选出合适的黄芩苷浓度。将缺氧乳腺癌干细胞MDA-MB-231随机分为10组:对照组、BL组(黄芩苷低浓度50.0 mg/L)、BM组(黄芩苷中浓度100.0 mg/L)、BH组(黄芩苷高浓度200.0 mg/L)、DDP组(顺铂)、M组(2-甲氧雌二醇)、BL+M组、BM+M组、BH+M组、DDP+M组。RT-PCR法检测HIF-1α、IGF-Ⅱ、L-selectin mRNA的表达,Western blot检测HIF-1α、IGF-Ⅱ、L-selectin蛋白的表达。结果 与对照组比较,DDP组细胞生长抑制率明显升高(P<0.05),不同浓度黄芩苷的细胞生长抑制率均明显升高(P<0.05)。与黄芩苷200.0 mg/L比较,其他浓度黄芩苷的细胞生长抑制率均明显降低(P<0.05),DDP组细胞生长抑制率明显升高(P<0.05)。与对照组比较,其余9组组HIF-1α、IGF-Ⅱ、L-selectin蛋白和mRNA表达均明显降低(P<0.05)。与BL组比较,BM组、BH组、BL+M组HIF-1α、IGF-Ⅱ、L-selectin蛋白和mRNA表达均明显降低(P<0.05)。与BM组比较,BM+M组HIF-1α、IGF-Ⅱ、L-selectin蛋白和mRNA表达均明显降低(P<0.05)。与BH组比较,BH+M组HIF-1α、IGF-Ⅱ、L-selectin蛋白和mRNA表达均明显降低(P<0.05)。结论 黄芩苷能抑制缺氧乳腺癌干细胞的增殖,可能通过调节HIF-1α/IGF-Ⅱ信号通路及L-selectin的表达抑制乳腺癌干细胞的增殖。 |
关键词: 黄芩苷 缺氧 乳腺癌干细胞 低氧诱导因子-1α 胰岛素样生长因子-Ⅱ L-选择素 |
DOI:10.3969/j.issn.1674-070X.2022.11.016 |
Received:December 07, 2021 |
基金项目:湖南省自然科学基金项目(2018JJ4096,2021JJ30418);湖南省教育厅一般项目(21C0248);湖南中医药大学科研基金项目(2019XJJJ007)。 |
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Effects of baicalin on proliferation of hypoxic triple-negative breast cancer stem cells and on HIF-1α, IGF-Ⅱ, and L-selectin |
XIAO Yujie,HUANG Lizhong,GONG Hui,DAI Xinjun,ZHU Xu,FENG Lei,WANG Ting |
(Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The Hospital of Hunan Institute of Chinese Medicine, Changsha, Hunan 410006, China;Central Hospital of Zhuzhou, Zhuzhou, Hunan 412007, China) |
Abstract: |
Objective To study the effects of baicalin on proliferation of hypoxic breast cancer cells MDA-MB-231, and on hypoxia-inducible factor-1α (HIF-1α), insulin-like growth factor-Ⅱ (IGF-Ⅱ) and L-selectin expression. Methods MTT assay was employed to detect inhibiting effect of different concentrations of baicalin (12.5, 25.0, 50.0, 100.0, 200.0 mg/L) on growth of hypoxic breast cancer stem cells MDA-MB-231, therefore identifying the appropriate baicalin concentration. The hypoxic breast cancer stem cells MDA-MB-231 were randomly divided into 10 groups: control group, BL group (baicalin low concentration 50.0 mg/L), BM group (baicalin medium concentration 100.0 mg/L), BH group (baicalin high concentration 200.0 mg/L), DDP group (cisplatin), M group (2-methoxyestradiol), BL+M group, BM+M group, BH+M group and DDP+M group. RT-PCR was employed to detect the expression of mRNA in HIF-1α, IGF-Ⅱ and L-selectin. Western blot was applied to detect the protein expression of HIF-1α, IGF-Ⅱ and L-selectin. Results Compared with the control group, the cell growth inhibition rate of DDP group and the cell growth inhibition rates at different concentrations of baicalin significantly increased (P<0.05). Compared with 200.0 mg/L baicalin, the cell growth inhibition rates of other concentrations of baicalin significantly decreased (P<0.05), while the cell growth inhibition rate of DDP group significantly increased (P<0.05). Compared with the control group, the protein and mRNA expression of HIF-1α, IGF-Ⅱ and L-selectin in the other 9 groups significantly decreased (P<0.05). Compared with the BL group, the protein and mRNA expression levels of HIF-1α, IGF-Ⅱ and L-selectin in the BM, BH and BL+M groups significantly decreased (P<0.05). Compared with the BM group, the protein and mRNA expression levels of HIF-1α, IGF-Ⅱ and L-selectin in the BM+M groups significantly decreased (P<0.05). Compared with the BH group, the protein and mRNA expression levels of HIF-1α, IGF-Ⅱ and L-selectin in the BH+M group significantly decreased (P<0.05). Conclusion Baicalin can inhibit the proliferation of hypoxic breast cancer stem cells. It may inhibit proliferation of breast cancer stem cells by regulating HIF-1α/IGF-Ⅱ signaling and L-selectin expression. |
Key words: baicalin hypoxia breast cancer stem cells hypoxia-inducible factor-1α insulin-like growth factor-Ⅱ L-selectin |
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