Department of Nephrology, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Technology of China, Chengdu, 610072, PR China.
Department of Nephrology, Affiliated Hospital of Chengdu University of TCM, Chengdu, 610075, PR China.
Biomed Pharmacother. 2018 Jan;97:1269-1274. doi: 10.1016/j.biopha.2017.11.064. Epub 2017 Nov 14.
Renal cell carcinoma (RCC) is a heterogeneous histological disease and the most common kidney cancer. The mortality rate of RCC remains high despite the improved treatment. Sinomenine is an isoquinoline extracted from Chinese medicinal plant Sinomenium acutum, famous for its ability to suppress several cancer cell types. Our research aimed to explore the anti-cancer potential of sinomenine in RCC. Results showed that sinomenine reduced the viability by reducing sphere-forming ability and enhancing pro-apoptosis effect in ACHN cells in a dose dependent manner. The expression levels of proliferation/apoptosis markers further validated the result. In addition, sinomenine significantly regulated the level of autophagy-related proteins with decreased expression of p62, and increased Beclin1 and LC3 II/LC3 I. Furthermore, phosphatidylinositol-3 kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR), the negatively regulated cell autophagy signaling pathway, was inhibited by sinomenine with decreased membrane translocation of AKT in ACHN cell lines. All in all, our study demonstrated that sinomenine promoted apoptosis in RCC via enhancing autophagy through PI3K/AKT/mTOR pathway.
肾细胞癌（RCC）是一种异质性组织学疾病，也是最常见的肾癌。尽管治疗有所改善，但 RCC 的死亡率仍然很高。青藤碱是从中国药用植物青风藤中提取的异喹啉，以抑制多种癌细胞类型而闻名。我们的研究旨在探讨青藤碱在 RCC 中的抗癌潜力。结果表明，青藤碱通过降低 ACHN 细胞的球体形成能力和增强促凋亡作用，以剂量依赖的方式降低细胞活力。增殖/凋亡标志物的表达水平进一步验证了这一结果。此外，青藤碱显著调节自噬相关蛋白的水平，降低 p62 的表达，增加 Beclin1 和 LC3 II/LC3 I。此外，PI3K/AKT/雷帕霉素靶蛋白（mTOR），即负调控细胞自噬的信号通路，被青藤碱抑制，AKT 在 ACHN 细胞系中的膜易位减少。总之，我们的研究表明，青藤碱通过 PI3K/AKT/mTOR 通路增强自噬促进 RCC 细胞凋亡。
