氟苯达唑通过G2/M期细胞周期阻滞和促凋亡作用抑制胶质瘤增殖。

Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis.

作者信息

Zhou Xumin, Liu Jumei, Zhang Jinming, Wei Yong, Li Hua

机构信息

1Department of Pathogen Biology and Experimental teaching center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease, School of Public Health, Southern Medical University, Guangzhou, 510515 China.

2Department of Respiration, Nanfang Hospital, Southern Medical University, Guangzhou, 510515 China.

出版信息

Cell Death Discov. 2018 Feb 14;4:18. doi: 10.1038/s41420-017-0017-2. eCollection 2018 Dec.

Flubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.

氟苯达唑是一种经美国食品药品监督管理局（FDA）批准的驱虫药，已广泛用于治疗肠道寄生虫。近年来，有报道称氟苯达唑具有抗癌活性。另一方面，关于氟苯达唑对胶质瘤的影响知之甚少。在此，我们展示了氟苯达唑对胶质瘤细胞的一种新作用。我们发现，氟苯达唑在体外抑制胶质瘤细胞系的细胞增殖并促进其细胞凋亡，通过腹腔注射在异种移植模型中抑制肿瘤生长。然而，氟苯达唑可能对细胞迁移没有影响。机制研究表明，氟苯达唑导致细胞周期停滞在G2/M期，这部分解释了其增殖受抑制的原因。一致地，氟苯达唑诱导胶质瘤细胞中P53表达，并降低细胞周期蛋白B1和磷酸化细胞分裂周期蛋白2（p-cdc2）的表达。此外，氟苯达唑通过调节经典凋亡蛋白BCL-2的表达促进细胞凋亡。这些观察结果表明，氟苯达唑通过影响细胞周期和内在凋亡信号在胶质瘤中发挥抗增殖和促凋亡作用，并提示氟苯达唑在胶质瘤治疗中的新用途。