Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent.
Trimebutine Promotes Glioma Cell Apoptosis as a Potential Anti-tumor Agent.
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曲美布汀作为潜在的抗肿瘤剂促进神经胶质瘤细胞凋亡。
DOI：
10.3389/fphar.2018.00664
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发表时间：
2018
影响因子：
5.6
通讯作者：
Pan HC
中科院分区：
文献类型：
--
作者：
Fan YP;Liu P;Xue WK;Zhao WJ;Pan HC
胶质瘤是最常见的原发性脑肿瘤，通常是致命的恶性肿瘤。尽管已有多种治疗选择，但它们与预后不良有关。曲美布汀是一种促动力学药物，主要用于治疗肠易激综合征等胃肠道疾病。然而，其对神经胶质瘤细胞的影响尚不清楚。在这里，我们使用不同浓度的曲美布汀治疗SHG44、U251和U-87 MG人胶质瘤/胶质母细胞瘤细胞。结合MTT实验、菌落形成实验、创面愈合实验、western blot和免疫荧光染色，评价曲美布汀对胶质瘤细胞的影响。结果表明，曲美布汀显著抑制细胞活力和集落形成。伤口愈合实验也表明对胶质瘤细胞的迁移有显著的抑制作用。此外，曲美布汀促进细胞凋亡，诱导Bcl-2下调，并伴有Bax上调。免疫荧光染色和western blot结果显示曲美布汀使活性Caspase-3水平升高。此外，曲美布汀降低AKT和ERK信号通路的激活。在裸鼠皮下U-87 MG细胞异种移植瘤中，曲美布汀显著抑制肿瘤生长。与对照相比，曲美布汀处理小鼠肿瘤切片中观察到更多的tunel阳性凋亡细胞。在曲美布汀处理的异种移植物组织中，Bcl-2减少，Bax上调，p-AKT和p-ERK信号通路受到干扰。我们的综合数据表明，曲美布汀可能潜在地应用于胶质瘤/胶质母细胞瘤的临床治疗。
Gliomas are the most common primary brain tumors with a usually fatal malignancy. They are associated with a poor prognosis although multiple therapeutic options have been available. Trimebutine is one of the prokinetic agents and it has been mainly used for treatment of disorders of the gastrointestinal (GI) tract such as irritable bowel syndrome. However, its effects on glioma cells remain unknown. Here, we used various concentrations of trimebutine to treat SHG44, U251, and U-87 MG human glioma/glioblastoma cells. And combined experiments of MTT, colony formation assay, and wound healing assay, as well as western blot and immunofluorescence staining were used to evaluate the effects of trimebutine on glioma cells. The results demonstrated that trimebutine significantly inhibited cell viability and colony formation. A significant inhibition of glioma cell migration was also indicated by wound healing assay. In addition, trimebutine promoted cell apoptosis and induced Bcl-2 downregulation, accompanied with Bax upregulation. Both immunofluorescence staining and western blot results showed that trimebutine increased the level of active Caspase-3. Moreover, trimebutine reduced the activation of both AKT and ERK signaling pathways. In subcutaneous U-87 MG cell xenograft tumors in nude mice, trimebutine significantly inhibited tumor growth. More TUNEL-positive apoptotic cells in tumor sections were observed in trimebutine-treated mice when compared to the vehicle control. Reduced Bcl-2 and upregulated Bax, as well as perturbed p-AKT and p-ERK signaling pathways were also observed in trimebutine-treated xenograft tissues. Our combined data indicated that trimebutine may be potentially applied for the clinical management of glioma/glioblastoma.
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影响因子：
4.3
作者：
Xu J;Hu C;Jiang Q;Pan H;Shen H;Schachner M
通讯作者：
Schachner M
影响因子：
15.9
作者：
Ostrom, Quinn T.;Gittleman, Haley;Barnholtz-Sloan, Jill S.
通讯作者：
Barnholtz-Sloan, Jill S.
影响因子：
4.7
作者：
Jiang, ZH;Zheng, X;Rich, KM
通讯作者：
Rich, KM
影响因子：
3.3
作者：
Guensberg, P;Wacheck, V;Jansen, B
通讯作者：
Jansen, B
影响因子：
--
作者：
Tsai JP;Lee CH;Ying TH;Lin CL;Lin CL;Hsueh JT;Hsieh YH
通讯作者：
Hsieh YH