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靛玉红抑制神经母细胞瘤 SH‑SY5Y 细胞的侵袭和转移。

Isatin inhibits the invasion and metastasis of SH‑SY5Y neuroblastoma cells in vitro and in vivo.

机构信息

Department of Neurobiology of Basic Experimental Center Medical College, Medical Department, Qingdao University, Qingdao, Shandong 266021, P.R. China.

Department of Biochemistry and Molecular Biology of Basic Experimental Center Medical College, Medical Department, Qingdao University, Qingdao, Shandong 266021, P.R. China.

出版信息

Int J Oncol. 2021 Jan;58(1):122-132. doi: 10.3892/ijo.2020.5144. Epub 2020 Nov 9.

Abstract

Indoline‑2,3‑dione or indole‑1H‑2,3‑dione, commonly known as isatin, is found in plants of genus Isatin and in Couropita guianancis aubl, and inhibits tumor cell proliferation through its antioxidant effects. The present study analyzed the effect of isatin on the malignant phenotype of neuroblastoma cells, and reported that isatin significantly inhibited neuroblastoma cell proliferation, invasion and migration in vitro in a dose‑dependent manner, and distant metastasis in tumor‑bearing mice. Mechanistically, isatin inhibited lysine‑specific histone demethylase (LSD)1 and reversed the blockade on p53, thereby activating the apoptotic pathway. The inhibitory effect of isatin on LSD1 may be mediated via direct binding and molecular docking or indirectly through the TGFβ/ERK/NF‑κB signaling pathway. Isatin also alleviated the renal and hepatic toxicity of cyclophosphamide in the tumor‑bearing mice, indicating its potential as a candidate drug as well as an adjuvant for treating metastatic neuroblastoma.

摘要

吲哚啉-2,3-二酮或吲哚-1H-2,3-二酮,通常称为靛红,存在于属植物和中,通过其抗氧化作用抑制肿瘤细胞增殖。本研究分析了靛红对神经母细胞瘤细胞恶性表型的影响,报道称靛红在体外以剂量依赖性方式显著抑制神经母细胞瘤细胞增殖、侵袭和迁移,并抑制荷瘤小鼠的远处转移。在机制上,靛红抑制赖氨酸特异性组蛋白去甲基化酶(LSD)1,并逆转对 p53 的阻断,从而激活凋亡途径。靛红对 LSD1 的抑制作用可能通过直接结合和分子对接介导,或通过 TGFβ/ERK/NF-κB 信号通路间接介导。靛红还减轻了荷瘤小鼠中环磷酰胺的肾和肝毒性,表明其具有作为治疗转移性神经母细胞瘤候选药物和辅助药物的潜力。

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