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那布卡辛通过调控 JAK2/STAT3 信号通路抑制脑胶质瘤细胞(U87)的增殖和迁移。

Napabucasin Inhibits Proliferation and Migration of Glioblastoma Cells (U87) by Regulating JAK2/STAT3 Signaling Pathway.

机构信息

Department of Neurosurgery, Faculty of Medicine, Beykent University, İstanbul 34398, Turkey.

Department of Gynecology and Obstetrics, Faculty of Medicine, Atatürk University, Erzurum 25240, Turkey.

出版信息

Medicina (Kaunas). 2024 Oct 19;60(10):1715. doi: 10.3390/medicina60101715.

DOI:10.3390/medicina60101715
PMID:39459502
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11509140/
Abstract

: Napabucasin (NP) was discovered as a natural compound that suppresses cancer stemness by inhibiting the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. In this study, the anti-proliferative and apoptotic effects of NP and the chemotherapy agent doxorubicin (DX), a natural compound, on glioblastoma cells (U87) were investigated. : In this study, the effects of NP and DX on cell viability on the glioblastoma U87 cell line were determined by MTT test. Expressions of Jak2/Stat3 genes were examined by qRT-PCR. Apoptosis was evaluated by Hoescht 33258 staining. Moreover, NP, its antagonistic-synergistic effects and IC50 doses of the combined treatment of DX were determined. : Napabucacin and doxorubicin were found to inhibit glioblastoma U87 cell proliferation. It was determined that NP applied in the range of 0.3-1 µM and its combination with DX killed almost all of the glioblastoma cells in 48 h of application. Additionally, it was observed that Jak2/Stat3 expressions downregulated. : These results show that NP suppresses the proliferation of glioblastoma cells. It was shown that the combination of NP and DX can prevent invasion of the U87 cell line due to its Jak2/Stat3 inhibitory effect. Since it can suppress Jak2/Stat3, an important cancer cell proliferation pathway in glioblastoma, the combination of NP and DX can be used as an alternative treatment agent. But no synergistic effect of NP and DX on the U87 cells of the glioblastoma cell line was observed.

摘要

Napabucasin (NP) 是一种天然化合物,通过抑制信号转导和转录激活因子 3 (STAT3) 信号通路来抑制癌症干细胞特性。本研究探讨了 NP 和天然化合物阿霉素 (DX) 对神经胶质瘤细胞 (U87) 的抗增殖和促凋亡作用。

在本研究中,通过 MTT 试验测定 NP 和 DX 对神经胶质瘤 U87 细胞系细胞活力的影响。通过 qRT-PCR 检测 Jak2/Stat3 基因的表达。通过 Hoechst 33258 染色评估细胞凋亡。此外,还确定了 NP 及其与 DX 的协同作用和联合治疗的 IC50 剂量。

结果表明,Napabucasin 和阿霉素均可抑制神经胶质瘤 U87 细胞增殖。结果表明,NP 以 0.3-1 μM 的浓度作用 48 小时,几乎可杀死所有神经胶质瘤细胞,其与 DX 的联合作用具有协同性。此外,观察到 Jak2/Stat3 表达下调。

这些结果表明 NP 可抑制神经胶质瘤细胞的增殖。NP 和 DX 的联合作用可通过抑制 Jak2/Stat3 来预防 U87 细胞系的侵袭。由于 NP 可抑制 Jak2/Stat3,而该通路是神经胶质瘤中癌细胞增殖的重要途径,因此 NP 和 DX 的联合治疗可作为替代治疗药物。但本研究未观察到 NP 和 DX 对神经胶质瘤 U87 细胞系的协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/f2872bf03ab3/medicina-60-01715-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/bb100cf3bd5b/medicina-60-01715-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/c067aed38492/medicina-60-01715-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/60add7091a29/medicina-60-01715-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/2b7a41ea472b/medicina-60-01715-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/2ceb399e9074/medicina-60-01715-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/cd93ffa44e06/medicina-60-01715-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/db4e863df07d/medicina-60-01715-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/3b33e2b34892/medicina-60-01715-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/f2872bf03ab3/medicina-60-01715-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/bb100cf3bd5b/medicina-60-01715-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/c067aed38492/medicina-60-01715-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/60add7091a29/medicina-60-01715-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/2b7a41ea472b/medicina-60-01715-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/2ceb399e9074/medicina-60-01715-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/cd93ffa44e06/medicina-60-01715-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/db4e863df07d/medicina-60-01715-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/3b33e2b34892/medicina-60-01715-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f763/11509140/f2872bf03ab3/medicina-60-01715-g009.jpg

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