Amniotic membrane promotes doxorubicin potency by suppressing SH-SY5Y neuroblastoma cell angiogenesis.

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-06-19 DOI:10.1186/s12885-025-14442-z

Ahmed M Abou-Shanab, Shaimaa Shouman, Alaa E Hussein, Ola A Gaser, Shireen Magdy, Eman Ashraf, Radwa Ayman Salah, Omaima Idris, Nagwa El-Badri

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引用次数: 0

Abstract

Background: Doxorubicin (DOX) remains a mainstay for neuroblastoma (NB) treatment, but side effects hamper efficacy. We previously showed that DOX induces SH-SY5Y NB cell angiogenesis via the PHD-2/HIF-1α axis. Adjuvant therapies offer a promising avenue to improved outcomes. Human amniotic membrane (hAM) extract (hAME) consists of various proteins that exhibit anti-cancer and anti-angiogenic properties. This study investigates hAME as a potential adjuvant for targeting NB angiogenesis when combined with DOX.

Methods: We used cellular, molecular, and biochemical assays to evaluate the antitumorigenic activities of hAME + DOX (D + E) treatment across key hallmarks of SH-SY5Y NB progression: proliferation, cell cycle, angiogenesis, invasiveness, differentiation, and cellular bioenergetics.

Results: D + E treatment significantly suppressed SH-SY5Y cell proliferation, induced cell cycle perturbations, and reduced viability, while protecting bone marrow stem cells and human skin fibroblast normal cells. D + E treatment also countered SH-SY5Y cell invasiveness and promoted a favorable mesenchymal-to-epithelial transition (MET). Importantly, D + E treatment modulated the SH-SY5Y cellular respiration, evidenced by halted glycolytic metabolism, potentially influencing a shift towards oxidative phosphorylation and boosted urea cycle progression. Mechanistically, D + E abrogated DOX's pro-angiogenic effects and inhibited SH-SY5Y cells' neo-vascularization in a chick embryo model.

Conclusions: These findings suggest hAME as a promising adjuvant therapy for NB, potentially offering an effective and safe treatment strategy by targeting multiple hallmarks of NB.

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羊膜通过抑制SH-SY5Y神经母细胞瘤细胞血管生成促进阿霉素效价。

背景：阿霉素（DOX）仍然是神经母细胞瘤（NB）治疗的主要药物，但副作用阻碍了疗效。我们之前发现DOX通过PHD-2/HIF-1α轴诱导SH-SY5Y NB细胞血管生成。辅助治疗为改善预后提供了一条有希望的途径。人羊膜提取物（hamme）由多种具有抗癌和抗血管生成特性的蛋白质组成。本研究探讨了hAME联合DOX作为靶向NB血管生成的潜在佐剂的作用。方法：我们使用细胞、分子和生化分析来评估hAME + DOX （D + E）治疗SH-SY5Y NB进展的关键标志的抗肿瘤活性：增殖、细胞周期、血管生成、侵袭性、分化和细胞生物能量学。结果：D + E处理显著抑制SH-SY5Y细胞增殖，诱导细胞周期紊乱，降低细胞活力，同时保护骨髓干细胞和人皮肤成纤维细胞正常细胞。D + E治疗还能对抗SH-SY5Y细胞的侵袭性，促进间质-上皮转化（MET）。重要的是，D + E处理调节SH-SY5Y细胞呼吸，通过停止糖酵解代谢证明，可能影响向氧化磷酸化的转变并促进尿素循环进程。在机制上，D + E消除了DOX的促血管生成作用，抑制了鸡胚模型中SH-SY5Y细胞的新血管形成。结论：这些研究结果表明，hAME作为NB的一种有希望的辅助治疗方法，可能通过针对NB的多种特征提供有效和安全的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.