Artesunate Inhibits the Proliferation and Migration of Cutaneous Squamous Cell Carcinoma by Regulating the SLC7A11-GPX4 Pathway via the p300-p53 Axis.

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Biomolecules & Therapeutics Pub Date : 2025-03-01 Epub Date: 2025-02-24 DOI:10.4062/biomolther.2024.156
Xinyan Huang, Wenxi Wang, Songzhao Zhang, Lili Li, Jihui Huang
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引用次数: 0

Abstract

The incidence of cutaneous squamous cell carcinoma (CSCC) is increasing rapidly. This study discussed the effects of artesunate (ART) on CSCC cell proliferation and migration via the solute carrier family 7 member 11 (SLC7A11)-glutathione peroxidase 4 (GPX4) pathway. MTT assessed cell viability and analyzed the IC50 value (69.26 μM). Accordingly, human CSCC cells (A431) were cultured in vitro, and treated with 70 μM ART, Ferrostatin-1, oe-SLC7A11, and C646, with cell biological behavior assessed. The potential targets of ART were predicted. p53 acetylation and protein stability and ART-p300 binding were examined. Thymusless nude mice were subcutaneously inoculated with A431 cells, and treated with ART and C646. ART-treated A431 cells showed weakened proliferation, migration, lactate dehydrogenase levels, oxidized glutathione/glutathione ratio, reactive oxygen species, malondialdehyde, and active Fe2+ levels, which could be reversed by suppressing ferroptosis. ART promoted p53 acetylation and protein stability and curbed the SLC7A11-GPX4 pathway by targeting p300. ART stimulated ferroptosis via the SLC7A11-GPX4 pathway, thereby repressing CSCC cell proliferation and migration, which were counteracted by p300 inhibition. ART regulated the SLC7A11-GPX4 pathway by up-regulating the p300-p53 axis, thereby hindering tumor growth in vivo. Collectively, ART inhibits CSCC proliferation and migration by modulating the SLC7A11-GPX4 pathway through the p300-p53 axis.

青蒿琥酯通过p300-p53轴调控SLC7A11-GPX4通路抑制皮肤鳞状细胞癌的增殖和迁移
皮肤鳞状细胞癌(CSCC)的发病率正在迅速上升。本研究通过溶质载体家族7成员11 (SLC7A11)-谷胱甘肽过氧化物酶4 (GPX4)途径探讨青蒿琥酯(ART)对CSCC细胞增殖和迁移的影响。MTT评估细胞活力并分析IC50值(69.26µM)。因此,体外培养人CSCC细胞(A431),并用70µM ART、Ferrostatin-1、e- slc7a11和C646处理,评估细胞生物学行为。预测了抗逆转录病毒治疗的潜在靶点。检测p53乙酰化、蛋白稳定性和ART-p300结合。用A431细胞皮下接种无胸腺裸鼠,用ART和C646处理。art处理的A431细胞增殖、迁移、乳酸脱氢酶水平、氧化谷胱甘肽/谷胱甘肽比值、活性氧、丙二醛和活性Fe2+水平减弱,可通过抑制铁下垂而逆转。ART通过靶向p300促进p53乙酰化和蛋白稳定性,抑制SLC7A11-GPX4通路。ART通过SLC7A11-GPX4途径刺激铁下垂,从而抑制CSCC细胞的增殖和迁移,这被p300抑制所抵消。ART通过上调p300-p53轴调控SLC7A11-GPX4通路,从而在体内抑制肿瘤生长。总的来说,ART通过p300-p53轴调节SLC7A11-GPX4通路来抑制CSCC的增殖和迁移。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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