Artesunate synergizes with sorafenib to induce ferroptosis in hepatocellular carcinoma.

Acta Pharmacologica Sinica
Zhong-Jie LiGuo-Dong Lu

Abstract

Sorafenib is the first-line medication for advanced hepatocellular carcinoma (HCC), but it can only extend limited survival. It is imperative to find a combination strategy to increase sorafenib efficacy. Artesunate is such a preferred candidate, because artesunate is clinically well-tolerated and more importantly both drugs can induce ferroptosis through different mechanisms. In this study we investigated the combined effect of sorafenib and artesunate in inducing ferroptosis of HCC and elucidated the involved molecular mechanisms. We showed that artesunate greatly enhanced the anticancer effects of low dose of sorafenib against Huh7, SNU-449, and SNU-182 HCC cell lines in vitro and against Huh7 cell xenograft model in Balb/c nude mice. The combination index method confirmed that the combined effect of sorafenib and artesunate was synergistic. Compared with the treatment with artesunate or sorafenib alone, combined treatment induced significantly exacerbated lipid peroxidation and ferroptosis, which was blocked by N-acetyl cysteine and ferroptosis inhibitors liproxstatin-1 and deferoxamine mesylate, but not by inhibitors of other types of cell death (z-VAD, necrostatin-1 and belnacasan). In Huh7 cells, we demonstrated that the...Continue Reading

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Citations

Feb 13, 2021·Oxidative Medicine and Cellular Longevity·Yue ChengXiaojing Liu
Jul 3, 2021·Cancers·Christina PfabNahed El-Najjar
Jul 9, 2021·Frontiers in Cell and Developmental Biology·Yuan ZhiKeqian Zhi
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Hui WangAnwen Shao
Sep 2, 2021·Journal of Hepatocellular Carcinoma·Hao LiaoZhiyu Xiao
Sep 21, 2021·Oncology Letters·Xiulan YangJie Zhang

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Methods Mentioned

BETA
xenograft
flow cytometry
MDA
flow
fluorescence microscopy
biopsy

Software Mentioned

ImageJ
Lipro
SPSS Statistics
SPSS
CompuSyn

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