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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,2022,42(11):1870-1875[点击复制] |
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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 |
| 投稿时间：2021-12-07 |
| 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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