Oncology Department, Zhangzhou Zhengxing Hospital, Zhangzhou, China.
Xiamen Institute of Union Respiratory Health, Xiamen, China.
Cancer Med. 2023 Jan;12(2):1643-1654. doi: 10.1002/cam4.4993. Epub 2022 Jul 4.
Kushenol A is natural flavonoid extract discovered in recent years, with potential anti-tumor activity. Its role in breast cancer is poorly understood.
To investigate biological function of Kushenol A in breast cancer (BC), Cell Counting Kit-8 assay, colony formation assay, flow cytometry, western blotting, qPCR analysis, and xenograft mouse model were performed.
We found that Kushenol A treatment reduced proliferative capability and induced G0/G1 phase cell cycle arrest and apoptosis of BC cells in a concentration-dependent manner. Besides, Kushenol A treatment contributed to the upregulation of apoptosis-related and cell cycle-associated genes. In nude mice, Kushenol A administration repressed BC xenograft tumor growth. Mechanistically, phosphorylation levels of AKT and mTOR were markedly attenuated in Kushenol A-treated BC cells; however, there were no significant differences in total AKT and mTOR expressions. Moreover, PI3K inhibitor combined with Kushenol A exhibited synergistic inhibitory activity on cell proliferation.
Taken together, our findings suggested that Kushenol A suppressed BC cell proliferation by modulating PI3K/AKT/mTOR signaling pathway. Kushenol A may be a promising therapeutic drug for treating BC.
苦参醇 A 是近年来发现的天然黄酮类提取物，具有潜在的抗肿瘤活性。但其在乳腺癌中的作用尚不清楚。
为了研究苦参醇 A 在乳腺癌（BC）中的生物学功能，我们进行了细胞计数试剂盒-8 检测、集落形成实验、流式细胞术、Western blot、qPCR 分析和异种移植小鼠模型实验。
我们发现苦参醇 A 处理可浓度依赖性地降低 BC 细胞的增殖能力，并诱导 G0/G1 期细胞周期阻滞和细胞凋亡。此外，苦参醇 A 处理可上调凋亡相关和细胞周期相关基因。在裸鼠中，苦参醇 A 给药抑制了 BC 异种移植肿瘤的生长。机制上，苦参醇 A 处理的 BC 细胞中 AKT 和 mTOR 的磷酸化水平明显降低，但总 AKT 和 mTOR 表达无明显差异。此外，PI3K 抑制剂与苦参醇 A 联合使用对细胞增殖具有协同抑制作用。
综上所述，我们的研究结果表明，苦参醇 A 通过调节 PI3K/AKT/mTOR 信号通路抑制 BC 细胞增殖。苦参醇 A 可能是治疗 BC 的一种有前途的治疗药物。
