二甲双胍、二氯乙酸和盐酸美金刚联合靶向治疗胶质母细胞瘤中的肿瘤细胞代谢。

Targeting Cancer Cell Metabolism with Metformin, Dichloroacetate and Memantine in Glioblastoma (GBM).

机构信息

Gazi University, Faculty of Medicine, Department of Medical Biology and Genetics, Ankara, Turkey.

出版信息

Turk Neurosurg. 2021;31(2):233-237. doi: 10.5137/1019-5149.JTN.29176-20.3.

DOI:10.5137/1019-5149.JTN.29176-20.3

PMID:33372258

Abstract

AIM

To investigate the effects of metformin, dichloroacetate (DCA), and memantine on T98G and U87-MG human glioblastoma (GBM) cells to target tumor cell metabolism in a multi-directional manner.

MATERIAL AND METHODS

IC50 levels for metformin, DCA, metformin+DCA and memantine were determined by MTT assay in T98G and U87-MG cells in vitro. Casp3, Bcl-2, Bax, c-Myc and GSK-3B protein expressions were investigated post treatments. Fifteen GBM+ tumor tissues were assessed for Casp-3, Bcl-2, Bad, Bax for apoptotic protein expression patterns.

RESULTS

Cancer cell metabolism targeting drugs metformin, DCA, metformin+DCA and memantine induced cytotoxicity in a dose-dependent manner in T98G and U87-MG cells. IC50 for memantine is found as 0.5 mM (p < 0.01) which is nearly 10 times lower concentration than that of metformin. Fifteen GBM+ tumor tissues had differential apoptotic protein expressions.

CONCLUSION

Memantine exerted anti-cancer mechanism of action in T98G and U87-MG cells, however, such a mechanism requires deeper investigation for GBM treatment.

摘要

目的

以多方位的方式靶向肿瘤细胞代谢，研究二甲双胍、二氯乙酸（DCA）和盐酸美金刚胺对 T98G 和 U87-MG 人胶质母细胞瘤（GBM）细胞的作用。

材料与方法

采用 MTT 法测定二甲双胍、DCA、二甲双胍+DCA 和盐酸美金刚胺在体外 T98G 和 U87-MG 细胞中的 IC50 水平。检测 Casp3、Bcl-2、Bax、c-Myc 和 GSK-3B 蛋白表达。对 15 例 GBM+肿瘤组织进行 Casp-3、Bcl-2、Bad、Bax 等凋亡蛋白表达模式的评估。