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A highly oxidized germacranolide from elephantopus tomentosus inhibits the growth of hepatocellular carcinoma cells by targeting EGFR in vitro and in vivo

癌症研究 体外 体内 蛋白激酶B 化学 肝细胞癌 细胞凋亡 吉马克兰内酯 PI3K/AKT/mTOR通路 MAPK/ERK通路 信号转导 生物 生物化学 生物技术 内酯
作者
Qian Li,Jiaqi Niu,Jianhuan Jia,Wei Xu,Ming Bai,Guo‐Dong Yao,Shao‐Jiang Song
出处
期刊:Bioorganic Chemistry [Elsevier]
卷期号:: 107007-107007
标识
DOI:10.1016/j.bioorg.2023.107007
摘要

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with high mortality and poor prognosis. WBDC-1 is a novel highly oxidized germacranolide from the Elephantopus tomentosus in our previous work, which has excellent anti-HCC activity, but the detailed mechanism is still unclear. In this study, we found that WBDC-1 was able to inhibit the proliferation and colony formation of Hep3B and HepG2 cells, as well as the cell migration ability and EMT. In addition, WBDC-1 showed no obvious toxicity to normal liver epithelial cells L-02. The potential targets of WBDC-1 were predicted by network pharmacology, and the following verified experiments showed that WBDC-1 exerted anti-HCC effect by targeting EGFR. Mechanismly, subsequent biological analysis showed that WBDC-1 can inhibit EGFR and its downstream RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways. Overexpression of EGFR reversed the anticancer properties of WBDC-1. Consistent with in vitro experiments, WBDC-1 was able to inhibit tumor growth and was non-toxic in xenograft tumor models. In summary, this study revealed a potential tumor suppressive mechanism of WBDC-1 and provided a novel strategy for HCC treatment. It also laid a foundation for further research on the anti-tumor effect of highly oxidized germacranolides.
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