Erastin对小鼠肝癌Hepa1-6细胞生长和转移的影响

Effect of Erastin on The Growth and Metastasis of Hepatocellular Carcinoma Hepa1-6 Cells in Mice

摘要

目的 通过体外细胞实验探讨铁死亡诱导剂Erastin对小鼠肝癌Hepa1-6细胞生长和转移的影响。方法 选取不同浓度Erastin作用于Hepa1-6细胞,用细胞增殖-毒性实验（MTT实验和CCK-8实验）检测Hepa1-6细胞的增殖和活性,平板克隆检测细胞的增殖能力,Transwell实验检测细胞的侵袭和迁移能力,划痕实验检测细胞的迁移能力。结果 随着Erastin浓度的增加,Hepa1-6细胞的增殖抑制率逐渐上升,存活率和增殖能力下降,迁移和侵袭的细胞数减少,迁移率降低。结论 Erastin能显著抑制小鼠肝癌 Hepa1-6细胞的增殖活性,对Hepa1-6细胞的侵袭和迁移能力也有抑制作用,且存在剂量依赖性。

Abstract

Objective To investigate the effect of Erastin on the growth and metastasis of hepatocellular carcinoma Hepa1-6 cells in vitro. Methods Hepa1-6 cells were treated with Erastin at different concentrations. The proliferation and activity of Hepa1-6 cells were assessed using cell proliferation-cytotoxicity assays, specifically the MTT assay and the CCK-8 assay. The proliferative capacity of the cells was evaluated through the plate colony formation assay. Additionally, the invasive and migratory abilities of the cells were investigated using the Transwell assay, with the migratory ability further examined through the scratch assay. Results As the concentration of Erastin increased, the inhibition rate of proliferation in Hepa1-6 cells progressively rose, while the survival rate and proliferative capacity declined correspondingly. Additionally, there was a reduction in both the number of migrating and invading cells, leading to decreased cellular mobility. Conclusion Erastin significantly inhibits the proliferation of Hepa1-6 cells and also reduces their invasion and migration in a dose-dependent manner.

关键词

erastin / 肝癌 / 增殖 / 侵袭 / 迁移

Key words

erastin / liver cancer / proliferation / invasion / migration

[1] Sun JH, Luo Q, Liu LL, et al.Liver cancer stem cell markers: Progression and therapeutic implications[J]. World J Gastroenterol, 2016, 22(13): 3547-3557.
[2] Anwaanwna D, Singh SK, Singh S, et al.Challenges in liver cancer and possible treatment approaches[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873(1): 188314.
[3] Stockwell BR, Friedmann angeli JP, Bayir H, et al. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease[J]. Cell, 2017, 171(2): 273-285.
[4] Li S, Huang Y.Ferroptosis: an iron-dependent cell death form linking metabolism, diseases, immune cell and targeted therapy[J]. Clin Transl Oncol, 2022, 24(1): 1-12.
[5] Zhao Y, Li Y, Zhang R, et al.The Role of Erastin in Ferroptosis and Its Prospects in Cancer Therapy[J]. Onco Targets Ther, 2020, (13): 5429-5441.
[6] Liu M, Fan Y, Li D, et al.Ferroptosis inducer erastin sensitizes NSCLC cells to celastrol through activation of the ROS-mitochondrial fission-mitophagy axis[J]. Mol Oncol, 2021, 15(8): 2084-2105.
[7] Liu CY, Chen KF, Chen PJ.Treatment of Liver Cancer[J]. Cold Spring Harb Perspect Med, 2015, 5(9): a021535.
[8] Teoh SL, Das S.The Emerging Role of the Hippo Pathway in Lung Cancers: Clinical Implications[J]. Curr Drug Targets, 2017, 18(16): 1880-1892.
[9] Desai A, Mohammed T, Patel KN, et al.5-Fluorouracil Rechallenge After Cardiotoxicity[J]. Am J Case Rep, 2020, (21): e924446.
[10] Liu Z, Zhang Y, Xiang Y, et al.Small-Molecule PROTACs for Cancer Immunotherapy[J]. Molecules, 2022, 27(17): 5439.
[11] Capelletti MM, Manceau H, Puy H, et al.Ferroptosis in Liver Diseases: An Overview[J]. Int J Mol Sci, 2020, 21(14): 4908.
[12] Wang L, Liu Y, Du T, et al.ATF3 promotes erastin-induced ferroptosis by suppressing system Xc[J]. Cell Death Differ, 2020, 27(2): 662-675.

基金资助

湖北科技学院医学部口腔与眼视光医学院专项科研基金项目（2021WG10）