Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Department of Urology, The Second People's Hospital of Hefei, Hefei, China.
Pharmacology. 2018;102(5-6):316-323. doi: 10.1159/000492935. Epub 2018 Oct 8.
Trametes robiniophila Murr (Huaier) has been used as an adjuvant therapy of tumor in traditional Chinese medicine for many years, but the underlying mechanisms are largely unknown. In the present study, we tested the inhibitory effect of Huaier extract on renal cancer 786-O cells and explored the possible mechanisms.
786-O cells were treated by gradient concentrations of Huaier extract, cell viability, invasion, migration and apoptosis were assessed by cell counting kit 8, cell scratch, transwell, and flow cytometry assay in vitro. The changes in protein level were detected by western blot analysis. Finally, the anticancer effect of Huaier was tested in vivo by nude mouse tumorigenicity assay.
Viability of 786-O cells was suppressed by Huaier in a time- and dose-dependent manner; cell invasion and migration were also dramatically inhibited. Flow cytometry assays showed that Huaier could induce cell apoptosis. Western blotting analysis indicated that Huaier suppressed the activation of PI3K/AKT/mTOR/p70S6K/4E-BP1 signaling pathway. We also found that Huaier could partly reverse the epithelialmesenchymal transition (EMT) process. In vivo experiment indicated that tumor growth in the xenograft mouse model was suppressed by Huaier.
Huaier plays an anticancer effect partially through the suppression of the PI3K/AKT/mTOR/p70S6K/4E-BP1 pathway and by reversing the EMT process. Huaier may act as an effective agent for treating renal cell carcinoma.
云芝(Huaier)多年来一直被用作中药辅助治疗肿瘤,但作用机制尚不清楚。本研究检测了云芝提取物对肾癌细胞 786-O 的抑制作用,并探讨了可能的机制。
用梯度浓度的云芝提取物处理 786-O 细胞,通过细胞计数试剂盒 8、细胞划痕、Transwell 和流式细胞术检测细胞活力、侵袭、迁移和凋亡。Western blot 分析检测蛋白水平的变化。最后,通过裸鼠肿瘤生成实验检测云芝的抗癌作用。
云芝提取物呈时间和剂量依赖性抑制 786-O 细胞活力;细胞侵袭和迁移也明显受到抑制。流式细胞术检测表明云芝可诱导细胞凋亡。Western blot 分析表明云芝抑制了 PI3K/AKT/mTOR/p70S6K/4E-BP1 信号通路的激活。我们还发现云芝可以部分逆转上皮间质转化(EMT)过程。体内实验表明云芝抑制了异种移植小鼠模型中的肿瘤生长。
云芝通过抑制 PI3K/AKT/mTOR/p70S6K/4E-BP1 通路和逆转 EMT 过程发挥抗癌作用。云芝可能是治疗肾细胞癌的有效药物。