TRAIL-conjugated silver nanoparticles sensitize glioblastoma cells to TRAIL by regulating CHK1 in the DNA repair pathway.,Neurological Research

当前位置： X-MOL 学术 › Neurol. Res. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

TRAIL-conjugated silver nanoparticles sensitize glioblastoma cells to TRAIL by regulating CHK1 in the DNA repair pathway.
Neurological Research ( IF 1.7 ) Pub Date : 2020-07-25 , DOI: 10.1080/01616412.2020.1796378
Ilknur Sur-Erdem _{1,

2} , Kerem Muslu ₁ , Nareg Pınarbası _{1,

2} , Mine Altunbek ₃ , Fidan Seker-Polat _{1,

2} , Ahmet Cingöz _{1,

2} , Serdar Onur Aydın ₂ , Mehmet Kahraman ₄ , Mustafa Culha ₃ , Ihsan Solaroglu _{1,

2} , Tugba Bagcı-Önder _{1,

2}

Affiliation

ABSTRACT

Objectives

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in cancer cells, but not in normal cells. Resistance of glioblastoma cells to TRAIL is a major obstacle for successful clinical treatment of TRAIL. Thus, there is an essential requirement for novel approaches to sensitize TRAIL resistance. Silver nanoparticles (AgNPs) are one of the most promising nanomaterials that show immense antitumor potential via targeting various cellular and molecular processes; however, the effects of AgNPs on TRAIL sensitivity in cancer cells remain unclear. Therefore, we hypothesized that TRAIL-conjugated AgNPs (TRAIL-AgNPs) can overcome TRAIL resistance through inducing death receptor activation in glioblastoma cells, but not normal cells.

Methods

In this study, the therapeutic effect of TRAIL-AgNPs is investigated by analyzing the cell viability, caspase activity, and CHK1 gene expression in T98 G TRAIL-Sensitive (TS) and T98 G TRAIL-Resistant (TR) glioblastoma cells.

Results

It is found that TRAIL-AgNPs are more toxic compared to TRAIL and AgNPs treatments alone on TR cells. While TRAIL and AgNPs alone do not enhance the caspase activity, conjugation of TRAIL to AgNPs increases the caspase activity in TR cells. Moreover, the TRAIL-AgNPs–treated TR cells show less CHK1 expression compared to the TRAIL treatment.

Conclusion

These results suggest that TRAIL sensitivity of TR cells can be enhanced by conjugation of TRAIL with AgNPs, which would be a novel therapeutic approach to sensitize TRAIL resistance.

中文翻译：

TRAIL 结合的银纳米颗粒通过调节 DNA 修复途径中的 CHK1 使胶质母细胞瘤细胞对 TRAIL 敏感。

摘要

目标

肿瘤坏死因子相关的凋亡诱导配体 (TRAIL) 选择性地触发癌细胞的凋亡，但不会触发正常细胞的凋亡。胶质母细胞瘤细胞对 TRAIL 的耐药性是成功临床治疗 TRAIL 的主要障碍。因此，对于使 TRAIL 抗性敏感的新方法存在基本要求。银纳米粒子 (AgNPs) 是最有前途的纳米材料之一，通过靶向各种细胞和分子过程显示出巨大的抗肿瘤潜力；然而，AgNPs 对癌细胞中 TRAIL 敏感性的影响仍不清楚。因此，我们假设 TRAIL 偶联的 AgNPs (TRAIL-AgNPs) 可以通过诱导胶质母细胞瘤细胞而非正常细胞中的死亡受体激活来克服 TRAIL 抗性。

方法

在本研究中，通过分析 T98 G TRAIL 敏感 (TS) 和 T98 G TRAIL 抗性 (TR) 胶质母细胞瘤细胞中的细胞活力、半胱天冬酶活性和 CHK1 基因表达来研究 TRAIL-AgNPs 的治疗效果。

结果

发现与单独对 TR 细胞进行 TRAIL 和 AgNPs 治疗相比，TRAIL-AgNPs 的毒性更大。虽然单独的 TRAIL 和 AgNPs 不会增强 caspase 活性，但 TRAIL 与 AgNPs 的结合会增加 TR 细胞中的 caspase 活性。此外，与TRAIL处理相比，TRAIL-AgNPs处理的TR细胞显示出较少的CHK1表达。