神经母细胞瘤是儿童时期常见的神经系统肿瘤，目前的治疗方法还不够。 HSP90 是一种分子伴侣蛋白，在癌症相关蛋白的调节中发挥着关键作用。 HSP90 抑制可能通过靶向癌症相关过程（如肿瘤生长、细胞增殖、转移和凋亡）发挥抗癌作用。因此，HSP90抑制是治疗各种类型癌症的一种有前景的策略，下一代抑制剂的开发可能会带来更有效、更安全的治疗。 XL-888 和 Debio0932 是下一代 HSP90 抑制剂，可以抑制癌症相关 HSP90 帮助正确折叠的客户蛋白的正确折叠和稳定。在本研究中，我们旨在研究XL-888和Debio0932在人神经母细胞瘤细胞SH-SY5Y中抗癌活性的综合分子途径。通过MTT法评估XL-888和Debio0932对神经母细胞瘤细胞系SH-SY5Y细胞的细胞毒作用。然后，通过定量实时聚合酶链反应（qRT-PCR）方法揭示了这些HSP90抑制剂对癌症中重要基因表达的影响。使用京都基因和基因组百科全书 (KEGG) 和基因本体论 (GO) 生物处理工具评估 qRT-PCR 数据。最后，通过Western blotting分析研究HSP90抑制剂对HSP27、HSP70和HSP90蛋白表达的影响。结果显示，XL-888和Debio0932在SH-SY5Y细胞中的迁移、侵袭、转移、血管生成和凋亡等许多癌症相关途径中具有调节作用。总之，它表明 HSP90 抑制剂可被视为治疗神经母细胞瘤和化疗耐药的有前途的候选药物。© 2024。作者。

Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.© 2024. The Author(s).