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野黄芩苷通过调节多个靶点的表达来治疗神经母细胞瘤。

Scutellarein treats neuroblastoma by regulating the expression of multiple targets.

作者信息

Zhai Chen-Yang, Fan Ji-Sheng, Zhang Rong-Ping

机构信息

Institute of Neuroscience Kunming Medical University Kunming China.

School of Pharmacy and Medical Sciences, Division of Health Sciences University of South Australia Adelaide Australia.

出版信息

Ibrain. 2023 May 13;10(3):345-355. doi: 10.1002/ibra.12100. eCollection 2024 Fall.

DOI:10.1002/ibra.12100
PMID:39346787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11427791/
Abstract

The aim of this study is to investigate the effect of scutellarein on the proliferation of neuroblastoma cells and the underlying mechanism. Six cell lines were used with drug intervention. Cell Counting Kit-8 was used to select the best, namely, SH-SY5Y, and then its IC value was determined. To further investigate the mechanism of scutellarin affecting SH-SY5Y proliferation, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of 11 factors. Scutellarin administration with 300 μM significantly reduced the number of SH-SY5Y, especially on the 3rd day of exposure to scutellarin. The IC value of scutellarin in SH-SY5Y cells was determined to be 117.8 μM. But the practical results showed that 300 μM was the optimal concentration of scutellarin. qRT-PCR further detected upregulated maternally expressed gene 3 (MEG3), oncogene c-Fos (c-FOS), and c-jun and downregulated M2 isoform of pyruvate kinase (PKM2), non-SMC Condensin I Complex Subunit H (NCAPH), epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1, and TGF-α, suggesting that scutellarin with 300 μM volume inhibited the survival of SH-SY5Y by regulating the expression of these 8 factors. Scutellarin could be a novel drug for the treatment of neuroblastoma, and its underlying mechanism may be related to the upregulated levels of MEG3, c-FOS, and c-jun and downregulated the expression of PKM2, NCAPH, EGFR, TGF-β1, and TGF-α.

摘要

本研究旨在探讨灯盏花素对神经母细胞瘤细胞增殖的影响及其潜在机制。使用六种细胞系进行药物干预。采用细胞计数试剂盒-8筛选出最佳细胞系,即SH-SY5Y,然后测定其半数抑制浓度(IC)值。为进一步研究灯盏花素影响SH-SY5Y增殖的机制,采用定量实时聚合酶链反应(qRT-PCR)检测11种因子的表达水平。给予300μM灯盏花素可显著减少SH-SY5Y细胞数量,尤其是在灯盏花素处理的第3天。灯盏花素在SH-SY5Y细胞中的IC值测定为117.8μM。但实际结果表明,300μM是灯盏花素的最佳浓度。qRT-PCR进一步检测到母源表达基因3(MEG3)、癌基因c-Fos(c-FOS)和c-jun上调,丙酮酸激酶M2亚型(PKM2)、非SMC凝聚素I复合体亚基H(NCAPH)、表皮生长因子受体(EGFR)、转化生长因子(TGF)-β1和TGF-α下调,提示300μM灯盏花素通过调节这8种因子的表达抑制SH-SY5Y细胞存活。灯盏花素可能是一种治疗神经母细胞瘤的新型药物,其潜在机制可能与MEG3、c-FOS和c-jun水平上调以及PKM2、NCAPH、EGFR、TGF-β1和TGF-α表达下调有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/56992e15c7be/IBRA-10-345-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/6813a9bc9fc6/IBRA-10-345-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/86fa892a3dc2/IBRA-10-345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/1ef735bd6f61/IBRA-10-345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/502d2f19a8f8/IBRA-10-345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/31ede0b4d1a6/IBRA-10-345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/56992e15c7be/IBRA-10-345-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/6813a9bc9fc6/IBRA-10-345-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/86fa892a3dc2/IBRA-10-345-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/1ef735bd6f61/IBRA-10-345-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/502d2f19a8f8/IBRA-10-345-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/31ede0b4d1a6/IBRA-10-345-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4276/11427791/56992e15c7be/IBRA-10-345-g005.jpg

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Curr Oncol Rep. 2022 Aug;24(8):1053-1062. doi: 10.1007/s11912-022-01270-8. Epub 2022 Apr 1.
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NCAPH promotes cell proliferation and inhibits cell apoptosis of bladder cancer cells through MEK/ERK signaling pathway.NCAPH 通过 MEK/ERK 信号通路促进膀胱癌细胞的增殖并抑制细胞凋亡。
Cell Cycle. 2022 Feb;21(4):427-438. doi: 10.1080/15384101.2021.2021050. Epub 2022 Jan 2.
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OCT1 Is a Poor Prognostic Factor for Breast Cancer Patients and Promotes Cell Proliferation via Inducing NCAPH.
OCT1 是乳腺癌患者的不良预后因素,并通过诱导 NCAPH 促进细胞增殖。
Int J Mol Sci. 2021 Oct 25;22(21):11505. doi: 10.3390/ijms222111505.
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Expression and Clinical Significance of the NCAPH, AGGF1, and FOXC2 Proteins in Serous Ovarian Cancer.NCAPH、AGGF1和FOXC2蛋白在浆液性卵巢癌中的表达及临床意义
Cancer Manag Res. 2021 Sep 21;13:7253-7262. doi: 10.2147/CMAR.S329688. eCollection 2021.
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Neuroblastoma.神经母细胞瘤。
Pediatr Blood Cancer. 2021 May;68 Suppl 2(Suppl 2):e28473. doi: 10.1002/pbc.28473.
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Molecular targeting therapies for neuroblastoma: Progress and challenges.神经母细胞瘤的分子靶向治疗:进展与挑战。
Med Res Rev. 2021 Mar;41(2):961-1021. doi: 10.1002/med.21750. Epub 2020 Nov 6.
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