Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
Biomed Res Int. 2019 Jun 23;2019:9241769. doi: 10.1155/2019/9241769. eCollection 2019.
Oroxylin A is a natural extract and has been reported to have a remarkable anticancer function. However, the mechanism of its anticancer activity remains not quite clear. In this study, we examined the inhibiting effects of Oroxylin A on breast cancer cell proliferation, migration, and epithelial-mesenchymal transition (EMT) and its possible molecular mechanism. The cytoactive and inflammatory factors were analyzed via Cell Counting Kit-8 assay and ELISA assay, respectively. Flow cytometry and western blotting were used to assess the cell proliferation. In addition, a wound healing assay and transwell assay were used to detect cell invasion and migration. qRT-PCR and western blot were employed to determine the effect of Oroxylin A on the EMT formation. Moreover, expression level of protein related to NF-B signaling pathway was determined by western blot. The results revealed that Oroxylin A attenuated the cytoactivity of MDA-MB-231 cells in a dose- and a time-dependent manner. Moreover, cell proliferation, invasion, and migration of breast cancer cells were inhibited by Oroxylin A compared to the control. The mRNA and protein expression levels of E-cadherin were remarkably increased while N-cadherin and Vimentin remarkably decreased. Besides, Oroxylin A suppressed the expression of inflammatory factors and NF-B activation. Furthermore, we also found that supplement of TNF- reversed the effects of Oroxylin A on the cell proliferation, invasion, migration, and EMT in breast cancer cells. Taken together, our results suggested that Oroxylin A inhibited the cell proliferation, invasion, migration, and EMT through inactivating NF-B signaling pathway in human breast cancer cells. These findings strongly suggest that Oroxylin A could be a therapeutic potential candidate for the treatment of breast cancer.
盐酸小檗碱 A 是一种天然提取物,已被报道具有显著的抗癌功能。然而,其抗癌活性的机制尚不完全清楚。在这项研究中,我们研究了盐酸小檗碱 A 对乳腺癌细胞增殖、迁移和上皮-间充质转化(EMT)的抑制作用及其可能的分子机制。通过细胞计数试剂盒-8 检测和 ELISA 检测分析细胞活性和炎症因子。采用流式细胞术和 Western blot 检测细胞增殖。此外,还使用划痕愈合实验和 Transwell 实验检测细胞侵袭和迁移。qRT-PCR 和 Western blot 用于确定盐酸小檗碱 A 对 EMT 形成的影响。此外,通过 Western blot 确定与 NF-B 信号通路相关的蛋白表达水平。结果表明,盐酸小檗碱 A 呈剂量和时间依赖性地减弱 MDA-MB-231 细胞的细胞活性。此外,与对照组相比,盐酸小檗碱 A 抑制了乳腺癌细胞的增殖、侵袭和迁移。E-钙粘蛋白的 mRNA 和蛋白表达水平显著增加,而 N-钙粘蛋白和波形蛋白显著减少。此外,盐酸小檗碱 A 抑制了炎症因子的表达和 NF-B 的激活。此外,我们还发现补充 TNF-α 可逆转盐酸小檗碱 A 对乳腺癌细胞增殖、侵袭、迁移和 EMT 的作用。总之,我们的研究结果表明,盐酸小檗碱 A 通过抑制 NF-B 信号通路抑制人乳腺癌细胞的细胞增殖、侵袭、迁移和 EMT。这些发现强烈表明,盐酸小檗碱 A 可能成为治疗乳腺癌的潜在治疗候选药物。