胰岛素瘤
GPX4
脂质过氧化
谷胱甘肽
化学
细胞凋亡
癌症研究
谷胱甘肽过氧化物酶
生物
生物化学
氧化应激
酶
胰腺
作者
Fengping Chen,Jing Lu,Biaolin Zheng,Yi Nan,Chunxiao Xie,Feiran Chen,Dafu Wei,Haixing Jiang,Shanyu Qin
标识
DOI:10.2174/0113816128289372240105041038
摘要
Background: Artesunate (ART) has been recognized to induce ferroptosis in various tumor phenotypes, including neuroendocrine tumors. We aimed to investigate the effects of ART on insulinoma and the underlying mechanisms by focusing on the process of ferroptosis. Methods: The CCK8 and colony formation assays were conducted to assess the effectiveness of ART. Lipid peroxidation, glutathione, and intracellular iron content were determined to validate the process of ferroptosis, while ferrostatin-1 (Fer-1) was employed as the inhibitor of ferroptosis. Subcutaneous tumor models were established and treated with ART. The ferroptosis-associated proteins were determined by western blot and immunohistochemistry assays. Pathological structures of the liver were examined by hematoxylin-eosin staining. Results: ART suppressed the growth of insulinoma both in vitro and in vivo. Insulinoma cells treated by ART revealed signs of ferroptosis, including increased lipid peroxidation, diminished glutathione levels, and ascending intracellular iron. Notably, ART-treated insulinoma cells exhibited a decline in the expressions of catalytic component solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). These alterations were negated by Fer-1. Moreover, no hepatotoxicity was observed upon the therapeutic dose of ART. Conclusion: Artesunate might regulate ferroptosis of insulinoma cells through the SLC7A11/GPX4 pathway.
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