Zhang Jun-Fei, Li Ya-Hong, Wang Zhao-Zhao, Jia Shu-Min, Yang Peng, Wang Rui-Nan, Zhao Jia-Nan, Yuan Ling, Nan Yi
Department of Emergency Medical, General Hospital of Ningxia Medical University, 804 South Shengli Street, Xingqing District, Yinchuan City, 750000, Ningxia, China.
Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, 750004, China.
Sci Rep. 2025 Sep 29;15(1):33429. doi: 10.1038/s41598-025-18912-z.
18β-Glycyrrhetinic acid (18β-GA) has a therapeutic effect on gastric cancer (GC), but its mechanism of action is still unclear. We analyzed the effects of 18β-GA on the proliferation, migration and invasion of GC cells using CCK technology, colony formation assay, wound healing assay and Transwell assay. BALB/c nude mice were used to establish subcutaneous transplantation models, orthotopic transplantation models and tail vein Liver metastasis models, and GC proliferation and metastasis models were constructed using zebrafish. After continuous treatment with 18β-GA, the inhibitory effect of drug on tumor was observed in vivo. Finally, western blot, immunohistochemistry (IHC) and immunofluorescence (IF) were used to detect the expression of key proteins in the TCTP/AKT/P53 signaling pathway and the key proteins in the cell apoptosis, cell cycle and EMT signaling pathways. Our in vitro and in vivo functional experiments showed that 18β-GA treatment could inhibit GC proliferation and metastasis, and the effect of 18β-GA alone was similar to that of TCTP knockdown, while the inhibition effect of 18β-GA combined with TCTP knockdown was the best. In GC, the expression of TCTP, p-AKT and Ki67 protein was significantly decreased after treatment with 18β-GA, while the expression of P53 protein was increased. In addition, 18β-GA treatment significantly increased the protein expression levels of Bax, P27, P21 and E-Cadherin, and decreased the protein expression levels of Bcl-2, Cyclin D1, N-Cadherin and Vimentin. Therefore, 18β-GA can promote cell apoptosis by inhibiting the TCTP/AKT/P53 signaling pathway, arrest the cell cycle and inhibit the proliferation and metastasis of GC.
18β-甘草次酸（18β-GA）对胃癌（GC）具有治疗作用，但其作用机制仍不清楚。我们使用CCK技术、集落形成试验、伤口愈合试验和Transwell试验分析了18β-GA对GC细胞增殖、迁移和侵袭的影响。使用BALB/c裸鼠建立皮下移植模型、原位移植模型和尾静脉肝转移模型，并使用斑马鱼构建GC增殖和转移模型。用18β-GA连续治疗后，在体内观察药物对肿瘤的抑制作用。最后，采用蛋白质免疫印迹法、免疫组织化学（IHC）和免疫荧光（IF）检测TCTP/AKT/P53信号通路中的关键蛋白以及细胞凋亡、细胞周期和EMT信号通路中的关键蛋白的表达。我们的体外和体内功能实验表明，18β-GA治疗可抑制GC的增殖和转移，单独使用18β-GA的效果与敲低TCTP相似，而18β-GA与敲低TCTP联合使用的抑制效果最佳。在GC中，用18β-GA治疗后，TCTP、p-AKT和Ki67蛋白的表达显著降低，而P53蛋白的表达增加。此外，18β-GA治疗显著增加了Bax、P27、P21和E-钙黏蛋白的蛋白表达水平，并降低了Bcl-2、细胞周期蛋白D1、N-钙黏蛋白和波形蛋白的蛋白表达水平。因此，18β-GA可通过抑制TCTP/AKT/P53信号通路促进细胞凋亡，使细胞周期停滞，并抑制GC的增殖和转移。
