γ干扰素和长春新碱的同时应用抑制原位神经母细胞瘤小鼠模型中的肿瘤生长。
Concurrent application of interferon-gamma and vincristine inhibits tumor growth in an orthotopic neuroblastoma mouse model.
机构信息
Department of Surgery, Stanford University, 453 Quarry Road, Palo Alto, CA, 94304, USA.
Department of Biomedical Engineering, Tufts University, 4 Colby Street, Medford, MA, 02155, USA.
出版信息
Pediatr Surg Int. 2023 Jul 27;39(1):241. doi: 10.1007/s00383-023-05523-w.
PURPOSE
Tumor-associated macrophages are present within neuroblastoma, and interferon-gamma (IFN-γ) can polarize macrophages into cancer-inhibiting M1 type. We hypothesize that treating neuroblastoma with interferon-gamma (IFN-γ) can suppress tumor growth, and the concurrent treatment with IFN-γ and vincristine can lead to enhanced tumor killing as compared to vincristine alone.
METHODS
We loaded IFN-γ or vincristine into silk biomaterials and recorded the amount released over time. Orthotopic, syngeneic neuroblastoma xenografts were generated by injecting 9464D cells into adrenal gland of C57BL/6 mice, and IFN-γ-loaded and/or vincristine-loaded silk biomaterials were implanted into the tumor once the tumors reached 100 mm. Drug release at different timepoints was measured and tumor growth after different treatments were compared.
RESULTS
1-2% of IFN-γ and 70% of vincristine were released from the biomaterials by the fifth day. Combining IFN-γ and vincristine significantly slowed tumor growth as compared to the controls (12.2 ± 2.7 days to reach 800 mm versus 5.7 ± 1.2 days, p = 0.01), and IFN-γ alone also delayed tumor growth as compared to the controls (10.9 ± 1.5 days versus 5.7 ± 1.2 days, p = 0.001). Hematoxylin and eosin staining demonstrated tumor necrosis adjacent to the drug-loaded silk biomaterials.
CONCLUSION
Local delivery of sustained release IFN-γ can inhibit neuroblastoma tumor growth by itself and in combination with vincristine.
目的
神经母细胞瘤中存在肿瘤相关巨噬细胞，干扰素-γ（IFN-γ）可以将巨噬细胞极化为抑制癌症的 M1 型。我们假设用干扰素-γ（IFN-γ）治疗神经母细胞瘤可以抑制肿瘤生长，并且与单独使用长春新碱相比，IFN-γ 与长春新碱同时治疗可以导致更强的肿瘤杀伤作用。
方法
我们将 IFN-γ 或长春新碱载入丝素生物材料中，并记录随时间的释放量。通过将 9464D 细胞注射到 C57BL/6 小鼠的肾上腺中来生成原位、同基因神经母细胞瘤异种移植物，并且一旦肿瘤达到 100mm 就将 IFN-γ 负载和/或长春新碱负载的丝素生物材料植入肿瘤中。测量不同时间点的药物释放情况，并比较不同治疗后的肿瘤生长情况。
结果
第 5 天，生物材料中释放了 1-2%的 IFN-γ 和 70%的长春新碱。与对照组相比，联合使用 IFN-γ 和长春新碱显著减缓了肿瘤生长（达到 800mm 的时间为 12.2±2.7 天，而对照组为 5.7±1.2 天，p=0.01），并且与对照组相比，IFN-γ 单独使用也延迟了肿瘤生长（达到 800mm 的时间为 10.9±1.5 天，而对照组为 5.7±1.2 天，p=0.001）。苏木精和伊红染色显示药物负载丝素生物材料附近的肿瘤坏死。
结论
局部持续释放 IFN-γ 可以单独或与长春新碱联合抑制神经母细胞瘤肿瘤生长。
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