癌症研究
川芎嗪
细胞凋亡
上皮-间质转换
化学
波形蛋白
转移
肿瘤微环境
癌变
药理学
癌症
医学
免疫学
内科学
病理
免疫组织化学
生物化学
肿瘤细胞
替代医学
作者
Xue Wang,Yan Tan,Yali Zhang,Zihui Xu,Bing Xu,Haimin Lei,Chengcheng Ding,Shuo Cheng,Xu Wang,Peng Wei,Zhaoyang Wang,Qiantai Mao,Chao Ai,Qian Hua
标识
DOI:10.1016/j.phrs.2020.105233
摘要
Hepatocellular carcinoma (HCC), with its high recurrence and metastasis rates, is a leading cause of cancer-related mortality, and available treatments include surgical resection and liver transplantation. TOGA is a novel conjugate combining 18β-glycyrrhetinic acid (GA), an active component of licorice, and tetramethylpyrazine, an effective component of Chuanxiong, with a small-molecule amino acid. This study examined the anti-hepatoma effects of TOGA and its specific mechanisms of action. We found that TOGA significantly prevented tumor growth in both nude mice carrying liver cancer xenograftsand mice carrying orthotopic tumors with little toxicity. NanoString analysis screening illustrated that TOGA may exert its anti-tumor effects by targeting interleukin (IL)-1R receptor 1 (IL-1R1). Further, TOGA significantly prevented the invasion and migration of HepG2 cells induced by tumor-associated macrophages (TAMs) or IL-1β, as confirmed by the reduced expression of the epithelial-mesenchymal transition (EMT)-related proteins Snail and Vimentin. Furthermore, IL-1β-induced activation of the IL-1R1/IκB/IKK/NF-κB signaling pathway in HepG2 cells was proved to be inhibited by TOGA. Taken together, TOGA effectively prevents the support of TAMs from fueling tumorigenesis through a mechanism related to the NF-κB pathway, and it may be a promising GA-modified drug for the treatment of HCC.
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