Shaanxi Key Laboratory of Degradable Biomedical Materials, Shaanxi R&D Center of Biomaterials, Fermentation Engineering, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi'an 710069, China.
Biotech and Biomed Research Institute, Northwest University, Taibai North Road 229, Xi'an 710069, China.
Nutrients. 2022 Apr 9;14(8):1564. doi: 10.3390/nu14081564.
Gastric cancer (GC) is the leading causes of cancer-related death worldwide. Surgery remains the cornerstone of gastric cancer treatment, and new strategies with adjuvant chemotherapy are currently gaining more and more acceptance. Ginsenoside Rh4 has excellent antitumor activity. Conversely, the mechanisms involved in treatment of GC are not completely understood. In this study, we certified that Rh4 showed strong anti-GC efficiency in vitro and in vivo. MTT and colony formation assays were performed to exhibit that Rh4 significantly inhibited cellular proliferation and colony formation. Results from the wound healing assay, transwell assays, and Western blotting indicated that Rh4 restrained GC cell migration and invasion by reversing epithelial-mesenchymal transition (EMT). Further validation by proteomic screening, co-treatment with disitertide, and SIX1 signal silencing revealed that SIX1, a target of Rh4, induced EMT by activating the TGF-β/Smad2/3 signaling pathway. In summary, our discoveries demonstrated the essential basis of the anti-GC metastatic effects of Rh4 via suppressing the SIX1-TGF-β/Smad2/3 signaling axis, which delivers a new idea for the clinical treatment of GC.
胃癌（GC）是全球癌症相关死亡的主要原因。手术仍然是胃癌治疗的基石，目前新的辅助化疗策略越来越被接受。人参皂苷 Rh4 具有优异的抗肿瘤活性。相反，治疗 GC 的机制尚不完全清楚。在这项研究中，我们证明 Rh4 在体外和体内均显示出很强的抗 GC 效率。MTT 和集落形成实验表明 Rh4 显著抑制细胞增殖和集落形成。划痕愈合实验、Transwell 实验和 Western blot 结果表明，Rh4 通过逆转上皮-间充质转化（EMT）抑制 GC 细胞迁移和侵袭。通过蛋白质组筛选、与 disitertide 联合处理和 SIX1 信号沉默的进一步验证表明，Rh4 的靶标 SIX1 通过激活 TGF-β/Smad2/3 信号通路诱导 EMT。总之，我们的发现通过抑制 SIX1-TGF-β/Smad2/3 信号轴，证明了 Rh4 抑制 GC 转移的重要基础，为 GC 的临床治疗提供了新的思路。
