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Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways.
Journal of Molecular Neuroscience ( IF 3.1 ) Pub Date : 2020-07-14 , DOI: 10.1007/s12031-020-01639-z
Ali Bagherian 1 , Rajab Mardani 2 , Bostan Roudi 1 , Mohsen Taghizadeh 3 , Hamid Reza Banfshe 4 , Amir Ghaderi 5 , Amirhossein Davoodvandi 6 , Samane Shamollaghamsari 6 , Michael R Hamblin 7, 8 , Hamed Mirzaei 3
Affiliation  

Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellar-curcumin (i.e., 20 μM and 50 μM) alone, and in combination with TMZ (50 μM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling–, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 μM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 μM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway–associated genes (β-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced.



中文翻译:

Nanomicellar-姜黄素和替莫唑胺的联合疗法通过 Wnt 信号通路对多形性胶质母细胞瘤进行体外治疗。

胶质母细胞瘤(GBM)是最严重的脑肿瘤,耐药率很高。Wnt 信号是 GBM 中非常重要的通路,可以激活/抑制其他通路,如细胞凋亡和自噬。在这项研究中,我们通过对自噬、细胞凋亡和 Wnt 信号通路的影响,评估了替莫唑胺 (TMZ) 加姜黄素或纳米胶束姜黄素的组合在体外抑制 GBM 生长的功效。单独使用两种浓度的姜黄素和纳米胶束姜黄素(即 20 μM 和 50 μM),并与 TMZ(50 μM)结合使用,在 U87 GBM 细胞系中诱导细胞毒性。通过定量逆转录酶聚合酶链反应 (qRT-PCR) 和蛋白质印迹评估 Wnt 信号、自噬和细胞凋亡相关基因。与对照相比,所有处理(除了单独的 20 μM 姜黄素)都显着降低了 U87 细胞的活力。姜黄素 (50 μM)、纳米胶束姜黄素单独和与 TMZ 组合显着降低 U87 细胞的侵袭和迁移。自噬相关蛋白(Beclin 1、LC3-I、LC3-II)显着增加。凋亡相关蛋白(Bcl-2 和 caspase 8)也显着增加,而 Bax 蛋白显着降低。Wnt 通路相关基因(β-catenin、cyclin D1、Twist 和 ZEB1)的表达水平显着降低。LC3-II) 显着增加。凋亡相关蛋白(Bcl-2 和 caspase 8)也显着增加,而 Bax 蛋白显着降低。Wnt 通路相关基因(β-catenin、cyclin D1、Twist 和 ZEB1)的表达水平显着降低。LC3-II) 显着增加。凋亡相关蛋白(Bcl-2 和 caspase 8)也显着增加,而 Bax 蛋白显着降低。Wnt 通路相关基因(β-catenin、cyclin D1、Twist 和 ZEB1)的表达水平显着降低。

更新日期:2020-07-14
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