EZH2 inhibition decreases neuroblastoma proliferation and in vivo tumor growth.
EZH2 inhibition decreases neuroblastoma proliferation and in vivo tumor growth.
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EZH2抑制降低神经母细胞瘤增殖和体内肿瘤生长。
DOI：
10.1371/journal.pone.0246244
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Beierle EA
中科院分区：
文献类型：
--
作者：
Bownes LV;Williams AP;Marayati R;Stafman LL;Markert H;Quinn CH;Wadhwani N;Aye JM;Stewart JE;Yoon KJ;Mroczek-Musulman E;Beierle EA
研究侵袭性神经母细胞瘤及其预后不良的机制对于寻找新的治疗靶点和提高生存率至关重要。已知Zust Homolog 2的增强子(EZH2)在支持多种癌症类型的恶性表型中起关键作用，而EZH2的敲除已被证明可减少神经母细胞瘤细胞的肿瘤发生。我们假设EZH2抑制剂GSK343将影响人类神经母细胞瘤的细胞增殖和生存能力。我们利用四个长期传代的神经母细胞瘤细胞系和两个患者来源的异黄素(PDX)来研究EZH2抑制剂GSK343对存活率、运动性、干性和体内肿瘤生长的影响。免疫印迹证实目标基因被击倒。GSK343治疗导致神经母细胞瘤细胞活力、迁移和侵袭以及干细胞数量显著降低。GSK343治疗了带有SK-N-BE(2)神经母细胞瘤的小鼠，与赋形剂治疗的小鼠相比，肿瘤生长显著减少。GSK343降低了长期传代神经母细胞瘤细胞系的活力和运动能力，并降低了神经母细胞瘤PDX细胞的干性。这些数据表明，进一步研究EZH2抑制剂在神经母细胞瘤细胞中的抗肿瘤作用的机制是必要的。
Investigation of the mechanisms responsible for aggressive neuroblastoma and its poor prognosis is critical to identify novel therapeutic targets and improve survival. Enhancer of Zeste Homolog 2 (EZH2) is known to play a key role in supporting the malignant phenotype in several cancer types and knockdown of EZH2 has been shown to decrease tumorigenesis in neuroblastoma cells. We hypothesized that the EZH2 inhibitor, GSK343, would affect cell proliferation and viability in human neuroblastoma. We utilized four long-term passage neuroblastoma cell lines and two patient-derived xenolines (PDX) to investigate the effects of the EZH2 inhibitor, GSK343, on viability, motility, stemness and in vivo tumor growth. Immunoblotting confirmed target knockdown. Treatment with GSK343 led to significantly decreased neuroblastoma cell viability, migration and invasion, and stemness. GSK343 treatment of mice bearing SK-N-BE(2) neuroblastoma tumors resulted in a significant decrease in tumor growth compared to vehicle-treated animals. GSK343 decreased viability, and motility in long-term passage neuroblastoma cell lines and decreased stemness in neuroblastoma PDX cells. These data demonstrate that further investigation into the mechanisms responsible for the anti-tumor effects seen with EZH2 inhibitors in neuroblastoma cells is warranted.
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影响因子：
3.7
作者：
Ferraro A;Boni T;Pintzas A
通讯作者：
Pintzas A
患者衍生的异种移植模型在癌症研究中的产生和应用。
影响因子：
4.6
作者：
Jung J;Seol HS;Chang S
通讯作者：
Chang S
影响因子：
4.3
作者：
Amatangelo, Michael D.;Garipov, Azat;Zhang, Rugang
通讯作者：
Zhang, Rugang
DOI：
10.1111/1440-1681.12382
发表时间：
2015-05-01
影响因子：
2.9
作者：
Ding, Muyang;Zhang, Hang;Gao, Yane
通讯作者：
Gao, Yane
影响因子：
11.5
作者：
Chase, Andrew;Cross, Nicholas C. P.
通讯作者：
Cross, Nicholas C. P.