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

doi:10.3969/j.issn.1006-7795.2026.02.003

Journal of Capital Medical University ›› 2026, Vol. 47 ›› Issue (2): 230-239.doi: 10.3969/j.issn.1006-7795.2026.02.003

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).

Abstract

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

CLC Number:

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

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