Panobinostat and its combination with 3-deazaneplanocin-A induce apoptosis and inhibit In vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines

Javier de la Rosa, Alejandro Urdiciain, Juan Aznar-Morales, B. Meléndez, J. Rey, M. Idoate, J. Castresana
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Abstract

Aim: Glioblastoma is the most malignant primary brain tumor. The treatment consists of surgery, with or without radiotherapy, and temozolomide, with a life expectancy of 12–15 months after diagnosis. Glioblastoma is resistant to conventional antitumor therapies. In this work, we present a preliminary in vitro study of two epigenetic drugs against GOS-3 glioblastoma cells. Methods: We used (1) panobinostat, a histone deacetylase inhibitor, and (2) 3-deazaneplanocin-A (DZ-Nep), an inhibitor of enhancer of zeste homolog 2 (EZH2) (enzyme of the polycomb repressor complex 2, polycomb group of proteins that trimethylate lysine 27 of histone 3-H3K27 me3-), as treatments that might modulate the PI3K pathway, affected in GOS-3 cells due to PTEN haploinsufficiency. The glioblastoma cell line GOS-3 was exposed to DZ-Nep and panobinostat treatments, separately and in combination, over a period of 2 days, after which cell migration, clonogenicity, and molecular expression characterization assays were performed. Results: Panobinostat alone or the combination of panobinostat plus DZ-Nep inhibited clonogenicity, metastasis, angiogenesis, epithelial–mesenchymal transition, and entry in the S phase of the cell cycle and induced apoptosis in GOS-3 glioblastoma cells. On the contrary, DZ-Nep inhibited cell migration (single treatment) and O(6)-methylguanine-DNA methyltransferase expression (DZ-Nep or double treatment). Conclusion: Panobinostat alone or the combination of panobinostat and DZ-Nep induce apoptosis and inhibit in vitro tumorigenesis and metastasis in GOS-3 glioblastoma cell lines.
Panobinostat及其联合3-deazaneplanocin-A诱导GOS-3胶质母细胞瘤细胞株凋亡并抑制其体外肿瘤发生和转移
目的:胶质母细胞瘤是恶性程度最高的原发性脑肿瘤。治疗包括手术,有或没有放射治疗,以及替莫唑胺,诊断后预期寿命为12-15个月。胶质母细胞瘤对常规的抗肿瘤治疗具有耐药性。在这项工作中,我们提出了两种表观遗传药物对GOS-3胶质母细胞瘤细胞的初步体外研究。方法:我们使用(1)组蛋白去乙酰化酶抑制剂panobinostat和(2)3-deazaneplanocin-A (DZ-Nep),一种zeste同源物2(多梳抑制复合物2的酶,多梳蛋白组3-H3K27 me3-的三甲基赖氨酸27的酶)的增强子抑制剂,作为可能调节由于PTEN单倍不足而影响GOS-3细胞的PI3K途径的治疗方法。将胶质母细胞瘤细胞系GOS-3分别或联合暴露于DZ-Nep和panobinostat处理2天,之后进行细胞迁移、克隆原性和分子表达表征分析。结果:Panobinostat单用或联合DZ-Nep可抑制GOS-3胶质母细胞瘤细胞的克隆性、转移、血管生成、上皮-间质转化、细胞周期进入S期,并诱导细胞凋亡。相反,DZ-Nep抑制细胞迁移(单处理)和O(6)-甲基鸟嘌呤- dna甲基转移酶表达(DZ-Nep或双处理)。结论:Panobinostat单用或与DZ-Nep联用均可诱导GOS-3胶质母细胞瘤细胞凋亡,抑制其体外肿瘤发生和转移。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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