PDF(Pubmed)
Abstract：
Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/β-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/β-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/β-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.
摘要：
富马酸替诺福韦酯（TDF）似乎可以预防慢性乙型肝炎病毒（HBV）患者的肝细胞癌（HCC）。然而,机制仍然鲜为人知。本研究旨在探讨TDF的作用和机制，富马酸替诺福韦艾拉酚胺（TAF），和恩替卡韦（ETV）对肝癌细胞的恶性特征。使用伤口愈合试验，transwell分析，基质胶transwell分析，和细胞计数试剂盒-8（CCK-8）测定，可以确定TDF/TAF，抑制迁移，入侵,HepG2细胞和Huh7细胞的增殖。为了调查机制，我们执行了TOP/FOP-Flash系统，蛋白质印迹,和RT-qPCR检测与TDF/TAF培养的肝癌细胞，发现与对照细胞相比，Wnt/β-catenin信号通路的活性较低。最后,丙型肝炎病毒p7反式调节蛋白3（p7TP3），肝癌的肿瘤抑制剂，在用TDF/TAF处理的HepG2细胞和Huh7细胞中显著增加。然而,恩替卡韦（ETV）处理的肝癌细胞的恶性特征没有显着差异，Wnt/β-catenin信号通路的活性，p7TP3的表达与对照组比较。最后，TDF/TAF可能是新的有希望的肝癌治疗策略，包括肝癌和肝母细胞瘤，通过Wnt/β-catenin信号通路，通过上调肿瘤抑制因子的表达，p7TP3。
