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氟苯达唑通过抑制 STAT3 和促进细胞周期停滞来发挥抗神经胶质瘤作用。

Flubendazole exhibits anti-glioblastoma effect by inhibiting STAT3 and promoting cell cycle arrest.

机构信息

Department of Medical Biology and Genetics, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03, Hradec Králové, Czech Republic.

Department of Medical Biochemistry, Faculty of Medicine in Hradec Králové, Charles University, Šimkova 870, 500 03, Hradec Králové, Czech Republic.

出版信息

Sci Rep. 2023 Apr 12;13(1):5993. doi: 10.1038/s41598-023-33047-9.

Abstract

Glioblastoma multiforme (GBM) belongs to most aggressive and invasive primary brain tumor in adults whose prognosis and survival remains poor. Potential new treatment modalities include targeting the cytoskeleton. In our study, we demonstrated that repurposed drug flubendazole (FLU) significantly inhibits proliferation and survival of GBM cells. FLU exerted its effect by affecting microtubule structure and our results also suggest that FLU influences tubulins expression to a certain degree. Moreover, FLU effects decreased activation of STAT3 and also partially inhibited its expression, leading to upregulation of p53 signaling pathway and subsequent cell cycle arrest at G2/M phase as well as caspase-dependent cell death in GBM cells. These results suggest FLU as a promising agent to be used in GBM treatment and prompting further testing of its effects on GBM.

摘要

多形性胶质母细胞瘤(GBM)属于成人中最具侵袭性和侵略性的原发性脑肿瘤,其预后和存活率仍然很差。潜在的新治疗方法包括靶向细胞骨架。在我们的研究中,我们证明了重新利用的药物氟苯达唑(FLU)可显著抑制 GBM 细胞的增殖和存活。FLU 通过影响微管结构发挥作用,我们的结果还表明,FLU 在一定程度上影响微管蛋白的表达。此外,FLU 的作用降低了 STAT3 的激活,也部分抑制了其表达,导致 p53 信号通路的上调,随后 GBM 细胞在 G2/M 期发生细胞周期阻滞以及 caspase 依赖性细胞死亡。这些结果表明 FLU 是一种很有前途的治疗 GBM 的药物,并促使进一步测试其对 GBM 的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fff3/10097688/e68c2cfa492a/41598_2023_33047_Fig1_HTML.jpg

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