Institute of Psychiatry and Neuroscience, Xinxiang Medical University, Xinxiang, China.
School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 211800, China.
Curr Mol Med. 2020;20(9):723-732. doi: 10.2174/1566524020666200409124258.
Astroglioma, one major form of brain tumors, has remained principally tough to handle for decades, due to the complexity of tumor pathology and the poor response to chemo- and radio-therapies.
Our previous study demonstrated that nifurtimox could regulate the signaling axis of AKT-GSK3β in various tumor types including the astroglioma U251 cells. Intriguingly, earlier case studies suggested that nifurtimox could possibly permeate the blood brain barrier and arrest neuroblastoma in the brain. These observations jointly encouraged us to explore whether nifurtimox would hinder the growth of astroglioma in vivo.
Our results exhibited that nifurtimox could competently hinder the development of astroglioma in the mouse brain as compared to temozolomide, the first line of drug for brain tumors. Meanwhile the surviving rate, as well as the body-weight was dramatically upregulated upon nifurtimox treatment, as compared to that of temozolomide. These findings offered nifurtimox as a better alternative drug in treating astroglioma in vivo.
Persistently, the manipulation of the signaling axis of AKT-GSK3β in astroglioma was found in line with earlier findings in neuroblastoma when treated with nifurtimox.
星形细胞瘤是脑肿瘤的主要形式之一，由于肿瘤病理学的复杂性以及对化疗和放疗反应不佳，几十年来一直难以处理。
我们之前的研究表明，硝呋替莫可调节包括星形细胞瘤 U251 细胞在内的多种肿瘤类型的 AKT-GSK3β 信号轴。有趣的是，早期的病例研究表明，硝呋替莫可能能够穿透血脑屏障并阻止神经母细胞瘤在大脑中生长。这些观察结果共同促使我们探索硝呋替莫是否会阻碍星形细胞瘤在体内的生长。
与用于治疗脑肿瘤的一线药物替莫唑胺相比，我们的结果表明硝呋替莫可有效地抑制小鼠大脑中的星形细胞瘤生长。同时，与替莫唑胺相比，用硝呋替莫治疗后，存活率以及体重显著提高。这些发现为硝呋替莫在体内治疗星形细胞瘤提供了更好的替代药物。
与神经母细胞瘤用硝呋替莫治疗时的早期发现一致，星形细胞瘤中 AKT-GSK3β 信号轴的操纵被发现符合要求。
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