Mutlu Melis, Tunca Berrin, Ak Aksoy Secil, Tekin Cagla, Egeli Unal, Cecener Gulsah
Department of Medical Biology, Faculty of Medicine, Uludag University, Bursa, Turkey.
Nutr Cancer. 2021;73(4):713-720. doi: 10.1080/01635581.2020.1765260. Epub 2020 May 14.
Glioblastoma (GB) is the most aggressive form of brain tumor. Despite the current treatment methods, the survival rate of patients is very low. Therefore, there is a need to develop new therapeutic agents. The migration and invasion capacity of GB cells is related to mesenchymal transition (MT) mechanism.
The effect of OLE on MT was determined by analysis of the Twist, Snail, Zeb1, N-cadherin and E-cadherin genes in the EMT mechanism. The effect of OLE on cell migration was determined by wound healing test.
2 mg/ml OLE reduced Twist, Snail, Zeb1 and N-cadherin expression and the combination of OLE + TMZ (2 mg/ml OLE + 350 mM TMZ) increased E-cadherin and reduced Twist, Zeb1 and N-cadherin. In addition, co-treatment with OLE increased TMZ-induced anti-invasion properties thought suppressing transcription factors of MT mechanism.
OLE can enhance the anti-MT activities of TMZ against GB and provide strong evidence that combined treatment with OLE and TMZ has the potential to be an effective alternative approach in GB therapy.
胶质母细胞瘤(GB)是最具侵袭性的脑肿瘤形式。尽管有目前的治疗方法,但患者的生存率非常低。因此,需要开发新的治疗药物。GB细胞的迁移和侵袭能力与间充质转化(MT)机制有关。
通过分析EMT机制中的Twist、Snail、Zeb1、N-钙黏蛋白和E-钙黏蛋白基因来确定OLE对MT的影响。通过伤口愈合试验确定OLE对细胞迁移的影响。
2mg/ml的OLE降低了Twist、Snail、Zeb1和N-钙黏蛋白的表达,并且OLE+TMZ(2mg/ml OLE+350mM TMZ)的组合增加了E-钙黏蛋白的表达,并降低了Twist、Zeb1和N-钙黏蛋白的表达。此外,与OLE联合治疗通过抑制MT机制的转录因子增加了TMZ诱导的抗侵袭特性。
OLE可以增强TMZ对GB的抗MT活性,并提供有力证据表明OLE和TMZ联合治疗有可能成为GB治疗中一种有效的替代方法。