Guo Zicheng, Wang Wang, Hu Weikang, You Wenjie, Wang Zijian
Department of Urology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.
Hubei Key Laboratory of Urological Diseases, Department of Urology, Cancer Precision Diagnosis and Treatment and Translational Medicine Hubei Engineering Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Pharmacol. 2025 Jul 18;16:1609354. doi: 10.3389/fphar.2025.1609354. eCollection 2025.
Plant-derived drugs (PDD) with remarkable anti-tumor activity and biosafety are highly desirable for clinical tumor chemotherapy. In this work, dihydromyricetin (DHM), a natural PDD extracted from ratten tea, was screened out to be a potential chemotherapeutic drug for muscle invasive bladder cancer (MIBC). The results of assays confirmed that DHM could effectively inhibit the proliferation, survival and migration of MIBC cells, and promote apoptosis ( < 0.05). M1 macrophage polarization was also observed after DHM chemotherapy. The hub genes in cell cycle and apoptosis signaling pathways were differential expressed, and the epithelial-mesenchymal transition (EMT) in MIBC cells was also reversed by DHM treatment. The effectiveness and biosafety evaluations of DHM chemotherapy were performed using a xenograft bearing mice model. The results revealed that DHM intravenous chemotherapy with a dose of 20 mg/kg for 7 times could significantly suppress the tumorigenesis of MIBC ( < 0.05), while triggered no obvious drug side effects. In conclusion, this work provided a PPD with remarkable and anti-tumor activity and biosafety, which could serve as a promising alternative for the application of MIBC chemotherapy.
具有显著抗肿瘤活性和生物安全性的植物源药物（PDD）是临床肿瘤化疗的理想选择。在这项研究中，从藤茶中提取的天然PDD二氢杨梅素（DHM）被筛选为肌肉浸润性膀胱癌（MIBC）的潜在化疗药物。实验结果证实，DHM可有效抑制MIBC细胞的增殖、存活和迁移，并促进细胞凋亡（<0.05）。DHM化疗后还观察到M1巨噬细胞极化。细胞周期和凋亡信号通路中的枢纽基因差异表达，DHM处理也逆转了MIBC细胞中的上皮-间质转化（EMT）。使用荷瘤小鼠模型对DHM化疗的有效性和生物安全性进行了评估。结果显示，20mg/kg剂量的DHM静脉化疗7次可显著抑制MIBC的肿瘤发生（<0.05），且未引发明显的药物副作用。总之，这项研究提供了一种具有显著生物安全性和抗肿瘤活性的PDD，可为MIBC化疗应用提供有前景的替代方案。
