Guo Tong, Wang Xitong, Zhang Gensheng, Xia Tian, Zhu Runzhi, Tou Jinfa
Department of Neonatal Surgery, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
National Clinical Research Center for Child Health, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Oncol. 2023 May 15;13:1160548. doi: 10.3389/fonc.2023.1160548. eCollection 2023.
Hepatoblastoma has an unsatisfactory prognosis, and traditional chemotherapy has strong side effects. Dihydromyricetin is a flavonoid extracted from a woody vine of the genus Serpentine in the family Vitaceae, with effects such as preventing alcoholic liver and reducing the incidence of liver cancer. However, the effect of DHM on hepatoblastoma and its specific pathway are still unclear.
The purpose of this study was to investigate the effects of DHM on children's hepatoblastoma and its related mechanisms.
CCK-8 assays were used to measure proliferation. Apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. Apoptotic cells were observed using Hoechst 33342 staining and fluorescence microscopy. Protein expression levels in HuH-6 and HepG2 cells were determined by western blotting.
We found that DHM was able to inhibit the growth and increase cellular mortality in HuH-6 and HepG2 cells. Furthermore, DHM decreased the intracellular ROS level and increased the expression of SOD1. ROS scavenger NAC promoted apoptosis, while the use of SOD1 inhibitor LCS-1 weakened the ROS scavenging effect of DHM , and to some extent reduced the killing effect of DHM on hepatoblastoma cells.
These results suggest that regulating SOD1/ROS pathway to induce apoptosis is one of the potential mechanisms of DHM as a tumor suppressor in hepatoblastoma. Therefore, DHM may be a novel candidate for inhibiting hepatoblastoma growth and deserves further study.
肝母细胞瘤预后不佳，传统化疗副作用大。二氢杨梅素是从葡萄科蛇葡萄属木质藤本植物中提取的一种黄酮类化合物，具有预防酒精性肝病和降低肝癌发病率等作用。然而，二氢杨梅素对肝母细胞瘤的作用及其具体途径仍不清楚。
本研究旨在探讨二氢杨梅素对儿童肝母细胞瘤的影响及其相关机制。
采用CCK-8法检测细胞增殖。通过流式细胞术分析细胞凋亡和活性氧（ROS）水平。使用Hoechst 33342染色和荧光显微镜观察凋亡细胞。采用蛋白质免疫印迹法检测HuH-6和HepG2细胞中的蛋白表达水平。
我们发现二氢杨梅素能够抑制HuH-6和HepG2细胞的生长并增加细胞死亡率。此外，二氢杨梅素降低了细胞内ROS水平并增加了SOD1的表达。ROS清除剂NAC促进细胞凋亡，而使用SOD1抑制剂LCS-1减弱了二氢杨梅素的ROS清除作用，并在一定程度上降低了二氢杨梅素对肝母细胞瘤细胞的杀伤作用。
这些结果表明，调节SODI/ROS途径诱导细胞凋亡是二氢杨梅素作为肝母细胞瘤肿瘤抑制因子的潜在机制之一。因此，二氢杨梅素可能是抑制肝母细胞瘤生长的新型候选药物，值得进一步研究。
