Glioblastoma is the most malignant and prevalent brain tumor in adults. It can grow and spread quickly causing harm to the brain health. One of the major challenges in treatment of glioblastoma is drug resistance. Use of synergistic combination of two drugs with different anti-tumor effects is nowadays highly considered in the development of effective therapeutic strategies for many malignancies. In the present study, we showed synergistic therapeutic efficacies of two chemical compounds, N-(4-hydroxyphenyl) retinamide (4HPR) and suberoylanilide hydroxamic acid (SAHA), for significant reduction in cell viability of rat C6 and human T98G glioblastoma cells. These compounds (4HPR and SAHA) were used alone or in synergistic combination for evaluating their various anti-tumor effects. The results showed that combination of 4HPR and SAHA significantly induced morphological and molecular features of astrocytic differentiation in C6 and T98G glioblastoma cells. Combination of 4HPR and SAHA proved to be an important therapeutic strategy for inhibiting cell growth and inducing differentiation in glioblastoma cells. Furthermore, combination of the two drugs showed more efficacies than either dug alone in reducing in vitro cell invasion (transwell assay), cell migration (wound healing assay), and angiogenesis (tube formation assay) due to down regulation of the molecules involved in these processes. The ultimate of goal of using this combination of drugs was induction of apoptosis. The results showed that these drugs in synergistic combination contributed highly to increases in morphological and molecular features of apoptotic death in the tumor cells. The results from molecular studies indicated that cell death occurred via activation of the extrinsic and intrinsic pathways of apoptosis in both C6 and T98G cells. The drugs in combination also contributed to dramatic inhibition of histone deacetylase 1, an important epigenetic player in promoting growth in glioblastoma cells. This novel combination of drugs should also be considered as a promising therapeutic strategy for the treatment of glioblastoma in vivo.

中文翻译：

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4HPR和SAHA的协同作用增强了胶质母细胞瘤细胞的抗肿瘤作用。

胶质母细胞瘤是成人中最恶性和最普遍的脑肿瘤。它可以快速生长和扩散，对大脑健康造成伤害。治疗胶质母细胞瘤的主要挑战之一是耐药性。如今，在开发针对许多恶性肿瘤的有效治疗策略时，高度重视使用两种具有不同抗肿瘤作用的药物的协同组合。在本研究中，我们显示了两种化合物N-（4-羟苯基）视黄酰胺（4HPR）和辛二酰苯胺基异羟肟酸（SAHA）的协同治疗功效，可显着降低大鼠C6和人T98G胶质母细胞瘤细胞的生存能力。这些化合物（4HPR和SAHA）可单独使用或协同使用以评估其各种抗肿瘤作用。结果表明，4HPR和SAHA的组合可显着诱导C6和T98G胶质母细胞瘤细胞星形细胞分化的形态和分子特征。4HPR和SAHA的组合被证明是抑制胶质母细胞瘤细胞生长和诱导分化的重要治疗策略。此外，由于降低了参与其中的分子的调节，两种药物的组合在减少体外细胞侵袭（transwell分析），细胞迁移（伤口愈合分析）和血管生成（管形成分析）方面显示出比单独使用两种药物更高的功效。流程。使用这种药物组合的最终目的是诱导细胞凋亡。结果表明，这些药物的协同组合对肿瘤细胞凋亡死亡的形态和分子特征的增加起了很大的作用。分子研究的结果表明，细胞死亡是通过激活C6和T98G细胞凋亡的外在和内在途径而发生的。这些药物的组合还有助于显着抑制组蛋白脱乙酰基酶1，这是促进成胶质细胞瘤细胞生长的重要表观遗传因素。这种新颖的药物组合也应被认为是体内治疗胶质母细胞瘤的有前途的治疗策略。这些药物的组合还有助于显着抑制组蛋白脱乙酰基酶1，这是促进成胶质细胞瘤细胞生长的重要表观遗传因素。这种新颖的药物组合也应被认为是体内治疗胶质母细胞瘤的有前途的治疗策略。这些药物的组合还有助于显着抑制组蛋白脱乙酰基酶1，这是促进成胶质细胞瘤细胞生长的重要表观遗传因素。这种新颖的药物组合也应被认为是体内治疗胶质母细胞瘤的有前途的治疗策略。