Liu Hua, Feng Xiao-De, Yang Beng, Tong Rong-Liang, Lu Yue-Jie, Chen Di-Yu, Zhou Lin, Xie Hai-Yang, Zheng Shu-Sen, Wu Jian
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University Zhejiang Province, China.
NHC Key Laboratory of Combined Multi-Organ Transplantation Hangzhou, China.
Am J Transl Res. 2019 Aug 15;11(8):4713-4725. eCollection 2019.
Dimethyl fumarate (DMF) is generally used to treat psoriasis and multiple sclerosis. In the present study, we aimed to investigate the effects of DMF on hepatocellular carcinoma progression and its mechanism of action. , cell viability was examined using CCK-8 assay; cell cycle was analyzed by flow cytometry; angiogenesis was detected using tube formation assay; and autophagic flux assay results were examined using fluorescence microscopy. We also used western blotting to explore the potential mechanisms. , tumor xenograft experiment was performed with nude mice, and liver function, renal function, and routine blood counts were assessed using biochemical tests. Dimethyl fumarate inhibited tumor growth and angiogenesis in hepatocellular carcinoma, both and . Dimethyl fumarate decreased autophagy in hepatocellular carcinoma cells. Treatment with DMF activated SOCS3, which led to repression of JAK1 and STAT3 phosphorylation. DMF inhibited cell proliferation, angiogenesis, and autophagy via activation of the SOCS3/JAK1/STAT3 signaling pathway. This finding may provide a novel approach for the treatment of hepatocellular carcinoma.
富马酸二甲酯（DMF）通常用于治疗银屑病和多发性硬化症。在本研究中，我们旨在研究DMF对肝细胞癌进展的影响及其作用机制。使用CCK-8法检测细胞活力；通过流式细胞术分析细胞周期；使用管形成试验检测血管生成；并使用荧光显微镜检查自噬通量试验结果。我们还使用蛋白质印迹法探索潜在机制。用裸鼠进行肿瘤异种移植实验，并使用生化试验评估肝功能、肾功能和血常规。富马酸二甲酯在体内和体外均抑制肝细胞癌的肿瘤生长和血管生成。富马酸二甲酯降低了肝癌细胞中的自噬。用DMF处理激活了SOCS3，这导致JAK1和STAT3磷酸化的抑制作用。DMF通过激活SOCS3/JAK1/STAT3信号通路抑制细胞增殖、血管生成和自噬。这一发现可能为肝细胞癌的治疗提供一种新方法。
