视网膜母细胞瘤（RB）是临床上常见的恶性肿瘤，通常发生在5岁以下的儿童中。恶性肿瘤转移频率的增加，以及延迟诊断和治疗导致治疗效果不佳。之前已经发现槲皮素在某些恶性肿瘤中可以抑制肿瘤生长。我们的研究旨在调查槲皮素在视网膜母细胞瘤发展中的作用和机制，以提供有效的临床治疗方法。使用Rb细胞系（WER1-RB1和Y79）培养不同浓度的槲皮素，然后确定细胞增殖、侵袭、凋亡和氧化应激情况。结果显示，槲皮素以剂量依赖的方式抑制Rb细胞的增殖和侵袭，并诱导细胞凋亡和氧化应激。此外，我们发现槲皮素处理使Rb细胞中miR-137的表达上调。miR-137抑制剂取消了槲皮素对Rb细胞进展的抑制作用。此外，双荧光素酶报告基因实验证实，纤维连接蛋白III结构域含蛋白5（FNDC5）是miR-137的靶点。miR-137的过表达抑制了Rb细胞的增殖和侵袭，并增强了细胞凋亡和氧化应激，而FNDC5的过表达取消了这些效应。此外，将WER1-RB1细胞注射到裸鼠体内建立异种移植瘤模型，然后给予50或100 mg/kg的槲皮素治疗。槲皮素治疗减轻了裸鼠体内异种移植瘤的生长。总之，槲皮素通过调节miR-137/FNDC5通路抑制Rb细胞的增殖和侵袭，并诱导凋亡和氧化应激。我们期望我们的研究能够为Rb的治疗提供有效方法。然而，槲皮素和miR-137可能在Rb细胞中产生非特异性效应，而且我们的研究仍存在一定限制。因此，我们将进一步研究槲皮素对Rb细胞中其他信号通路的影响，并探索联合治疗在后续实验中的应用，以为使用槲皮素治疗Rb提供严密的研究基础。版权所有 © 2023 Elsevier Inc. 发表。

Retinoblastoma (RB) constitutes a prevalent malignancy in clinic and usually occurs in children under the age of 5 years old. The increased frequency of malignant tumor metastases and the delayed diagnosis and treatment caused unsatisfactory therapeutic efficiency. Quercetin was formerly identified to impede tumor growth in certain malignancies. Our study attempted to investigate the effects and mechanisms of quercetin in Rb development, in order to provide an effective clinical therapeutic approach. Rb cell lines (WER1-RB1 and Y79) were incubated with different concentrations of quercetin, and then cell proliferation, invasion, apoptosis, and oxidative stress were determined. It was showed that quercetin restrained Rb cell proliferation and invasion, and induced cell apoptosis and oxidative stress in a dose dependent manner. Moreover, we found that quercetin incubation upregulated miR-137 expression in Rb cells. MiR-137 inhibition abrogated quercetin-mediated inhibition of Rb cell progression. Furthermore, dual-luciferase reporter gene assay validated that fibronectin type III domain-containing protein 5 (FNDC5) was a target for miR-137. MiR-137 overexpression restrained proliferation and invasion, and enhanced apoptosis and oxidative stress in Rb cells, whereas FNDC5 overexpression abrogated these effects. Additionally, nude mice were injected with WER1-RB1 cells to establish a xenograft tumor model, and then treated with 50 or 100 mg/kg quercetin. Quercetin treatment mitigated xenograft tumor growth in nude mice. In conclusion, quercetin restrained proliferation and invasion, and induced apoptosis and oxidative stress in Rb cells through regulating the miR-137/FNDC5 pathway. We expected that our study could provide an effective approach for Rb treatment. However, quercetin and miR-137 may have off-target effects in Rb cells, and our study still has certain limitations. Therefore, we will investigate the effects of quercetin on other signaling pathways in Rb cells and explore the application of combination therapy in follow-up experiments, in order to provide a rigorous research basis for the treatment of Rb with quercetin.Copyright © 2023. Published by Elsevier Inc.