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杨梅素通过下调基质金属蛋白酶(MMP)-2/9 的活性抑制乳腺癌转移。

Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9.

机构信息

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.

College of Life Science, Beijing Normal University, Beijing, China.

出版信息

Phytother Res. 2018 Jul;32(7):1373-1381. doi: 10.1002/ptr.6071. Epub 2018 Mar 13.

Abstract

Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 ± 15.41% after treatment with 50 mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.

摘要

肿瘤转移是导致乳腺癌死亡的主要原因。杨梅素是一种天然多酚,存在于茶、酒和浆果中。杨梅素对乳腺癌转移的药效作用和分子机制尚不清楚。在这里,我们研究了杨梅素对 MDA-Mb-231Br 细胞活力、迁移、侵袭以及 4T1 小鼠肺转移模型的影响。通过 Western blot 分析和定量实时聚合酶链反应分别分析 MMP-2/9 蛋白表达和 ST6GALNAC5 表达。通过划痕愈合和 Boyden 小室侵袭实验检测细胞迁移和侵袭。通过肺转移模型评估体内抗转移作用。杨梅素显著降低 MMP-2/9 的活性和 ST6GALNAC5 的 mRNA 水平。此外,迁移、侵袭和黏附被有效抑制,呈浓度依赖性。另一方面,与载体小鼠相比,用杨梅素处理的小鼠显示出较小的肿瘤结节,用 50mg/kg 杨梅素处理后,肿瘤结节仅为 17.78±15.41%。总之,杨梅素可通过抑制 MMP-2/9 蛋白表达和 ST6GALNAC5 的表达,显著阻断 MDA-Mb-231Br 细胞的侵袭,并在小鼠模型中抑制肺转移,提示杨梅素可作为治疗乳腺癌的潜在候选药物。

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