重新定位奈非那韦：AIM2炎症小体相关的抗胶质母细胞瘤作用
Repurposing Nelfinavir: AIM2 inflammasome-associated anti-tumor effects in Glioblastoma.
摘要(中文译文)
奈非那韦（NFR）最初是作为抗人类免疫缺陷病毒的抗逆转录病毒药物开发的，已在多种恶性肿瘤中显示出抗癌特性；然而，其在胶质母细胞瘤（GBM）中的治疗潜力在很大程度上尚未被探索。在本研究中，我们使用一套全面的实验模型研究了NFR在GBM中的抗肿瘤作用，包括已建立的GBM细胞系、GBM细胞系来源的球状体、患者来源的原代胶质瘤细胞以及患者来源的胶质瘤类器官。我们进一步在这些平台上评估了NFR与标准化疗药物卡铂和多柔比星联合使用的抗肿瘤潜力。体外分析显示，NFR显著抑制GBM细胞增殖，并诱导凋亡性和坏死性细胞死亡。此外，我们发现NFR处理与GBM细胞中AIM2炎症小体的激活相关，并可能有助于NFR诱导的抗胶质瘤效应。然而，仅AIM2炎症小体的激活并非诱导其在GBM中抗肿瘤效应所必需。总之，我们的研究结果强调NFR是GBM一个有前景的治疗候选药物，通过抗增殖和促死亡机制发挥作用。
Abstract
Nelfinavir (NFR), originally developed as an antiretroviral agent for the human immunodeficiency virus, has demonstrated anti-cancer properties across various malignancies; however, its therapeutic potential in Glioblastoma (GBM) remains largely unexplored. In the present study, we investigated the anti-tumor effects of NFR in GBM using a comprehensive panel of experimental models, including established GBM cell lines, GBM cell line-derived spheroids, patient-derived primary glioma cells, and patient-derived glioma organoids. We further evaluated the anti-tumor potential of NFR in combination with standard chemotherapeutic agents, carboplatin and doxorubicin, across these platforms. In vitro analyses revealed that NFR significantly inhibits GBM cell proliferation and induces both apoptotic and necrotic cell death. Additionally, we identified that NFR treatment is associated with activation of the AIM2 inflammasome in GBM cells and may contribute to NFR-induced anti-glioma effects. However, activation of the AIM2 inflammasome alone is not essential to induce its anti-tumor effects in GBM. Collectively, our findings highlight NFR as a promising therapeutic candidate for GBM, exerting its effects through anti-proliferative and pro-death mechanisms.
如何引用
AMA
Durgesh Meena, Lipika Sha, Shalini Chhipa, Priya Solanki, Sushmita Jha. Repurposing Nelfinavir: AIM2 inflammasome-associated anti-tumor effects in Glioblastoma.. Biochimica et biophysica acta. Molecular basis of disease. 2027; doi:10.1016/j.bbadis.2026.168428.
APA
Durgesh Meena, Lipika Sha, Shalini Chhipa, Priya Solanki, Sushmita Jha (2027). Repurposing Nelfinavir: AIM2 inflammasome-associated anti-tumor effects in Glioblastoma.. Biochimica et biophysica acta. Molecular basis of disease. https://doi.org/10.1016/j.bbadis.2026.168428
GB/T 7714
Durgesh Meena, Lipika Sha, Shalini Chhipa, Priya Solanki, Sushmita Jha. Repurposing Nelfinavir: AIM2 inflammasome-associated anti-tumor effects in Glioblastoma.[J]. Biochimica et biophysica acta. Molecular basis of disease, 2027 doi:10.1016/j.bbadis.2026.168428.
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