Zhang Yaqin, Dong Weijie, Zhu Junying, Wang Lizhu, Wu Xinjian, Shan Hong
Department of Radiology, The 5th Affiliated Hospital of Sun Yat-sen University, No. 52 Meihua Dong Road, Zhuhai, 519000 Guangdong Province People's Republic of China.
Neurosurgery Department, The 1st Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan No. 2 Road, Guangzhou, 510030 Guangdong Province People's Republic of China.
Cell Biosci. 2017 Oct 30;7:56. doi: 10.1186/s13578-017-0184-0. eCollection 2017.
Diffuse intrinsic pontine glioma is an infiltrative, often high-grade glioma of the brainstem that is not amenable to surgical resection. The current treatment of DIPG by radiation therapy showed dramatically improvement of patient's condition, however, the tumor recurs rapidly. More and more studies are focused on the genetic and epigenetic drivers of DIPGs, which may provide more and more novel therapy target for DIPG. EZH2 has been proved to be a potential therapeutic target for H3K27M-mutant pediatric gliomas recently. Meanwhile, BET family protein is a hot target in many different types of cancers, including DIPG. In this study, we performed the treatment of both EZH2 and BET inhibitor for DIPG cells.
The combination of these two inhibitors exhibited better inhibition of the tumor growth both in vitro and in vivo compared to use the inhibitor individually. This inhibition was performed by blocking the proliferation and promoting the cell apoptosis. Meanwhile, combination treatment of these two inhibitors would also affect the epigenetic markers which were abnormal in the tumors of the certain set of genes.
Thus we provided a novel therapy strategy for clinical treatment of DIPG.
弥漫性脑桥内生型胶质瘤是一种浸润性的、通常为高级别的脑干胶质瘤，无法通过手术切除。目前通过放射治疗弥漫性脑桥内生型胶质瘤可显著改善患者病情，然而，肿瘤会迅速复发。越来越多的研究聚焦于弥漫性脑桥内生型胶质瘤的基因和表观遗传驱动因素，这可能为弥漫性脑桥内生型胶质瘤提供越来越多新的治疗靶点。最近已证明EZH2是H3K27M突变型儿童胶质瘤的潜在治疗靶点。同时，BET家族蛋白是包括弥漫性脑桥内生型胶质瘤在内的许多不同类型癌症的热门靶点。在本研究中，我们对弥漫性脑桥内生型胶质瘤细胞进行了EZH2和BET抑制剂联合治疗。
与单独使用抑制剂相比，这两种抑制剂联合使用在体外和体内均表现出对肿瘤生长更好的抑制作用。这种抑制作用是通过阻断增殖和促进细胞凋亡来实现的。同时，这两种抑制剂联合治疗还会影响某些基因肿瘤中异常的表观遗传标记。
因此，我们为弥漫性脑桥内生型胶质瘤的临床治疗提供了一种新的治疗策略。
