STAT3抑制剂WP1066对MYCN扩增型神经母细胞瘤增殖的抑制作用

doi:10.3969/j.issn.1006-7795.2026.02.003

首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (2): 230-239.doi: 10.3969/j.issn.1006-7795.2026.02.003

• 肿瘤演进机制与临床防治 • 上一篇下一篇

STAT3抑制剂WP1066对MYCN扩增型神经母细胞瘤增殖的抑制作用

贾安娜^1#,张瑶^1#,占丽平²,张璇¹,战世佳¹,郭金鑫¹,洪恩宇¹,张文欣¹,郭永丽¹,常艳^1*

1. 国家儿童医学中心首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室北京市儿科研究所儿童耳鼻咽喉头颈外科疾病实验室，北京 100045；2. 鹰潭一八四医院普外二科，江西鹰潭 335000

收稿日期:2025-10-23 修回日期:2025-11-23 出版日期:2026-04-21 发布日期:2026-04-21
通讯作者: 常艳 E-mail:changyan809@ ccmu. edu. cn
基金资助:
北京市自然科学基金项目（7252046），国家自然科学基金项目（82402039），北京市卫生健康委员会改革与发展项目（EYGF-ENT-02）。

Inhibitory effects of STAT3 inhibitor WP1066 on proliferation of MYCN amplified neuroblastoma cells

Jia Anna^1#, Zhang Yao^1#, Zhan Liping², Zhang Xuan¹, Zhan Shijia¹, Guo Jinxin¹, Hong Enyu¹, Zhang Wenxin¹, Guo Yongli¹, Chang Yan¹

1. Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Childrens Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; 2. The Second Department of General Surgery, Yingtan 184 Hospital, Yingtan 335000, Jiangxi Province, China

Received:2025-10-23 Revised:2025-11-23 Online:2026-04-21 Published:2026-04-21
Supported by:
This study was supported by Beijing Natural Science Foundation (7252046), National Natural Science Foundation of China (82402039), Funding for Reform and Development of Beijing Municipal Health Commission (EYGF-ENT-02).

摘要/Abstract

摘要： 目的探究小分子药物WP1066对MYCN扩增型神经母细胞瘤（neuroblastoma，NB）增殖的抑制作用及分子机制。方法从26种获美国食品药品监督管理局（Food and Drug Administration，FDA）批准或处于临床试验阶段的儿童药物中，筛选出对MYCN扩增型NB细胞SK-N-BE（2）杀伤效果最显著的药物WP1066。使用不同浓度梯度WP1066处理MYCN扩增型NB细胞SK-N-BE（2）、IMR32，MYCN非扩增型NB细胞SH-SY5Y、SK-N-AS，人视网膜上皮细胞hTERT RPE-1，采用CellTiter-Glo、结晶紫染色、克隆形成等实验检测细胞增殖及活力，Caspase3/7试剂盒检测细胞凋亡，Western blotting检测信号转导和转录激活因子3（signal transducer and activator of transcription 3，STAT3）和p-STAT3蛋白水平的表达，实时荧光定量反转录聚合酶链式反应（real-time quantitative reverse transcription polymerase chain reaction, RT-qPCR）检测抗凋亡分子Bcl-2 mRNA水平的表达。结果 CellTiter-Glo结果显示，WP1066对MYCN扩增型NB细胞SK-N-BE（2）、IMR32杀伤效果显著（P＜0.05），相同浓度下对MYCN非扩增型NB细胞SH-SY5Y、SK-N-AS，人视网膜上皮细胞hTERT RPE-1的影响不显著。结晶紫染色和克隆形成实验也显示出同样的实验结果。Caspase3/7检测细胞凋亡结果显示，WP1066显著促进MYCN扩增型NB细胞SK-N-BE（2）凋亡（P＜0.05），但是对MYCN非扩增型NB细胞SH-SY5Y没有显著影响。在机制方面，小分子药物WP1066通过抑制SK-N-BE（2）细胞p-STAT3水平及其下游抗凋亡分子Bcl-2的表达水平（P＜0.05），进而抑制NB细胞活力。结论 WP1066对MYCN扩增型NB细胞增殖有显著的抑制作用，有望成为MYCN扩增型NB的候选治疗药物。

关键词: 神经母细胞瘤, MYCN基因扩增, WP1066, 信号转导和转录激活因子3, 磷酸化STAT3, 细胞增殖

Abstract: Objective To investigate the inhibitory effects and molecular mechanisms of the small molecule drug WP1066 on MYCN amplified neuroblastoma (NB) cells. Methods Among 26 pediatric drugs approved by the Food and Drug Administration (FDA) or in clinical trials, WP1066 demonstrated the most potent cytotoxic effect against MYCN amplified NB cells SK-N-BE(2). After treatment with different concentration gradients of WP1066, cell proliferation and viability were detected with CellTiter-Glo, crystal violet staining, and colony formation assays in MYCN amplified NB cells SK-N-BE(2) and IMR32, MYCN non-amplified NB cells SH-SY5Y and SK-N-AS, and human retinal pigment epithelial cells hTERT RPE-1. Apoptosis was detected with Caspase3/7 assay. The expression levels of signal transducer and activator of transcription 3(STAT3) and p-STAT3 proteins were detected with Western blotting, and the expression level of the anti-apoptotic molecule Bcl-2 mRNA was detected with real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results CellTiter-Glo results showed that WP1066 had a significant killing effect on MYCN-amplified NB cells SK-N-BE(2) and IMR32(P<0.05), but had no significant effect on MYCN non-amplified NB cells SH-SY5Y and SK-N-AS, and human retinal pigment epithelial cells hTERT RPE-1 at the same concentration. Crystal violet staining and colony formation experiments also showed the same results. Caspase3/7 apoptosis assay showed that WP1066 significantly promoted apoptosis in MYCN amplified NB cells SK-N-BE(2) (P<0.05), but had no significant effect on MYCN non-amplified NB cells SH-SY5Y. At the mechanism level, the small molecule drug WP1066 affected the activity of NB cells by inhibiting the p-STAT3 level in SK-N-BE(2) cells and regulating the expression level of Bcl-2(P<0.05), an anti-apoptotic molecule downstream of p-STAT3. Conclusion WP1066 has a significant inhibitory effect on the proliferation of MYCN amplified NB cells and is expected to become a candidate therapeutic drug for MYCN amplified NB.

Key words: neuroblastoma, MYCN gene amplification, WP1066, signal transducer and activator of transcription 3 (STAT3), phosphorylated STAT3, cell proliferation

中图分类号:

贾安娜, 张瑶, 占丽平, 张璇, 战世佳, 郭金鑫, 洪恩宇, 张文欣, 郭永丽, 常艳. STAT3抑制剂WP1066对MYCN扩增型神经母细胞瘤增殖的抑制作用[J]. 首都医科大学学报, 2026, 47(2): 230-239.

Jia Anna, Zhang Yao, Zhan Liping, Zhang Xuan, Zhan Shijia, Guo Jinxin, Hong Enyu, Zhang Wenxin, Guo Yongli, Chang Yan. Inhibitory effects of STAT3 inhibitor WP1066 on proliferation of MYCN amplified neuroblastoma cells[J]. Journal of Capital Medical University, 2026, 47(2): 230-239.

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STAT3抑制剂WP1066对MYCN扩增型神经母细胞瘤增殖的抑制作用

Inhibitory effects of STAT3 inhibitor WP1066 on proliferation of MYCN amplified neuroblastoma cells

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