Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells
Suppression of glioblastoma by a drug cocktail reprogramming tumor cells into neuronal like cells
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通过药物混合物将肿瘤细胞重编程为神经元样细胞来抑制胶质母细胞瘤
DOI：
10.1038/s41598-019-39852-5
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发表时间：
2019-03-05
影响因子：
4.6
通讯作者：
Pei, Gang
中科院分区：
文献类型：
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作者：
Gao, Longfei;Huang, Shichao;Pei, Gang
胶质母细胞瘤（GBM）是成人脑内最常见、最具侵袭性的恶性肿瘤。即使采用目前的标准治疗，包括手术切除，术后放疗和替莫唑胺（Temo）化疗，GBM患者的中位生存期仍然很差。将肿瘤细胞重编程为非恶性细胞可能是恶性肿瘤（包括GBM）的一种有前途的治疗策略。基于先前使用小分子将星形胶质细胞重编程为神经元细胞的研究，在此我们进一步鉴定了三种常用药物（法舒地尔、曲尼司特和Temo）的FTT混合物，以将在含血清或无血清培养基中培养的患者来源的GBM细胞重编程为神经元样细胞。FTT处理的GBM细胞表现出神经元样形态，表达神经元基因，表现出神经元电生理特性，并显示出减弱的恶性。更重要的是，FTT混合物比单独的Temo更显著地抑制GBM患者来源的异种移植物中的肿瘤生长和延长的存活。我们的研究提供了临床前证据，神经元重编程药物鸡尾酒可能是一个有前途的策略，以改善现有的治疗GBM。
Glioblastoma (GBM) is the most common and aggressive malignant tumor in adult brain. Even with the current standard therapy including surgical resection followed by postoperative radiotherapy and chemotherapy with temozolomide (Temo), GBM patients still have a poor median survival. Reprogramming of tumor cells into non-malignant cells might be a promising therapeutic strategy for malignant tumors, including GBM. Based on previous studies using small molecules to reprogram astrocytes into neuronal cells, here we further identified a FTT cocktail of three commonly used drugs (Fasudil, Tranilast, and Temo) to reprogram patient-derived GBM cells, either cultured in serum containing or serum-free medium, into neuronal like cells. FTT-treated GBM cells displayed a neuronal like morphology, expressed neuronal genes, exhibited neuronal electrophysiological properties, and showed attenuated malignancy. More importantly, FTT cocktail more significantly suppressed tumor growth and prolonged survival in GBM patient derived xenograft than Temo alone. Our study provided preclinical evidence that the neuronal reprogramming drug cocktail might be a promising strategy to improve the existing treatment for GBM.