金雀异黄素通过影响干性和 p53 依赖性 VEGFA/Dll4/Notch1 通路抑制射频消融不足后的肝癌细胞血管生成。
Amarogentin Inhibits Liver Cancer Cell Angiogenesis after Insufficient Radiofrequency Ablation via Affecting Stemness and the p53-Dependent VEGFA/Dll4/Notch1 Pathway.
机构信息
Department of Hepatopancreatobiliary Surgery, Third Hospital of Mianyang-Sichuan Mental Health Center, Mianyang, Sichuan 621000, China.
Key Laboratory of Molecular Biology for Infectious Diseases of the Ministry of Education of China, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
出版信息
Biomed Res Int. 2020 Oct 20;2020:5391058. doi: 10.1155/2020/5391058. eCollection 2020.
BACKGROUND
Whether and how amarogentin suppresses the angiogenesis effect in liver cancer cells after insufficient radiofrequency ablation (iRFA) are still poorly studied.
METHODS
The number of liver cancer stem cells (LCSCs) and the level of vascular endothelial growth factor A (VEGFA) were assessed in liver cancer tissue after iRFA. Then, CD133-positive cells were detected in iRFA models of HepG2 and Huh7 cell lines treated with amarogentin. Tube formation assays were applied to observe the antiangiogenesis effects of amarogentin. In addition, the angiogenesis-related molecules p53, delta-like ligand 4 (Dll4), and Notch1 were detected in the iRFA cells and mouse models treated with amarogentin.
RESULTS
The mRNA and protein expression levels of CD133 and VEGFA were significantly higher in the residual liver cancer tissue than in the liver cancer tissues treated by hepatectomy. Amarogentin then markedly decreased the percentage of CD133-positive cells in the iRFA model in both HepG2 and Huh7 cell lines. The number of tubules formed by human umbilical vein endothelial cells (HUVECs) was significantly decreased by amarogentin. Inversely, the antiangiogenesis effect of amarogentin was counteracted after p53 silencing in the iRFA cell models.
CONCLUSION
Amarogentin prevents the malignant transformation of liver cancer after iRFA via affecting stemness and the p53-dependent VEGFA/Dll4/Notch1 pathway to inhibit cancer cell angiogenesis.
背景
阿魏酸瑞香素是否以及如何抑制射频消融（iRFA）后肝癌细胞的血管生成作用仍研究甚少。
方法
检测 iRFA 后肝癌组织中的肝癌干细胞（LCSC）数量和血管内皮生长因子 A（VEGFA）水平。然后，检测经阿魏酸瑞香素处理的 HepG2 和 Huh7 细胞系 iRFA 模型中 CD133 阳性细胞。应用管形成实验观察阿魏酸瑞香素的抗血管生成作用。此外，检测 iRFA 细胞和经阿魏酸瑞香素处理的小鼠模型中与血管生成相关的分子 p53、Delta-like 配体 4（Dll4）和 Notch1。
结果
与肝切除术治疗的肝癌组织相比，残留肝癌组织中 CD133 和 VEGFA 的 mRNA 和蛋白表达水平明显更高。阿魏酸瑞香素显著降低了 HepG2 和 Huh7 细胞系 iRFA 模型中 CD133 阳性细胞的百分比。阿魏酸瑞香素显著减少了人脐静脉内皮细胞（HUVEC）形成的管数。相反，在 iRFA 细胞模型中沉默 p53 后，阿魏酸瑞香素的抗血管生成作用被拮抗。
结论
阿魏酸瑞香素通过影响干性和 p53 依赖性 VEGFA/Dll4/Notch1 通路抑制癌细胞血管生成，防止 iRFA 后肝癌的恶性转化。
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