Silver Nanotriangles and Chemotherapeutics Synergistically Induce Apoptosis in Glioma Cells via a ROS-Dependent Mitochondrial Pathway.
Silver Nanotriangles and Chemotherapeutics Synergistically Induce Apoptosis in Glioma Cells via a ROS-Dependent Mitochondrial Pathway.
复制标题
银纳米三角形和化疗药物通过 ROS 依赖性线粒体途径协同诱导胶质瘤细胞凋亡
DOI：
10.2147/ijn.s267120
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发表时间：
2020
影响因子：
8
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Yang H;Chen W;Ma J;Zhao J;Li D;Cao Y;Liu P
纳米材料与化疗药物的协同作用为肿瘤的治疗提供了一种新的策略。银纳米三角形（AgNTs）在纳米医学中表现出一些独特的性能。银基纳米材料与抗肿瘤药物协同作用治疗胶质瘤的研究很少。材料与方法制备了壳聚糖包被的AgNTs，并用透射电镜、紫外-可见光谱和x射线衍射对其进行了表征。通过MTT法评估环磷酰胺（CTX）、5-氟尿嘧啶（5-FU）、奥沙利铂（OXA）、阿霉素（DOX）或吉西他滨（GEM）联合AgNTs对不同胶质瘤细胞系（U87、U251和C6）的抗胶质瘤作用，筛选出广谱、协同抗胶质瘤活性最强的药物。流式细胞术检测细胞内活性氧（ROS）水平、线粒体膜电位（MMP）和细胞凋亡。进一步研究了ROS清除剂和C-jun n -末端激酶（JNK）、p38和细胞外信号调节激酶1/2通路的特异性抑制剂协同作用的可能潜在机制。结果合成的AgNTs以三角形和截断三角形为主，平均边长为125 nm。未观察到AgNTs联合CTX的协同抗胶质瘤作用，AgNTs与5-FU之间的协同作用是细胞类型特异性的。AgNTs与OXA、DOX或GEM联用在多种胶质瘤细胞系中均表现出协同作用，其中AgNTs与GEM联用的协同作用最强。ROS清除剂n -乙酰半胱氨酸和JNK抑制剂SP600125可显著减弱这种协同作用引起的细胞活力下降、MMP缺失和凋亡率升高。结论我们的研究结果表明，AgNTs和GEM联合使用具有广谱和有效的协同抗胶质瘤活性，这是由于细胞凋亡是由ros依赖的线粒体途径介导的，JNK可能参与了该途径。
Background The synergistic effect of nanomaterials and chemotherapeutics provides a novel strategy for the treatment of tumors. Silver nanotriangles (AgNTs) exhibited some unique properties in nanomedicine. Studies on the synergy of silver-based nanomaterials and anti-tumor drugs against gliomas are rare. Materials and Methods Chitosan-coated AgNTs were prepared, followed by characterization using transmission electron microscopy, ultraviolet-visible spectroscopy and X-ray diffraction. The anti-glioma effect of cyclophosphamide (CTX), 5-fluorouracil (5-FU), oxaliplatin (OXA), doxorubicin (DOX) or gemcitabine (GEM) combined with AgNTs in different glioma cell lines (U87, U251 and C6) was assessed by the MTT assay to screen out a drug with the most broad-spectrum and strongest synergistic anti-glioma activity. The intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) and cell apoptosis were detected by flow cytometry. The possible underlying mechanisms of the synergy were further investigated with ROS scavenger and specific inhibitors of C-jun N-terminal kinase (JNK), p38 and extracellular signal-regulated kinase 1/2 pathways. Results The synthesized AgNTs were mainly triangular and truncated triangular with an average edge length of 125 nm. A synergistic anti-glioma effect of AgNTs combined with CTX was not observed, and the synergism between AgNTs and 5-FU was cell type-specific. AgNTs combined with OXA, DOX or GEM displayed synergistic effects in various glioma cell lines, and the combination of AgNTs and GEM showed the strongest synergistic activity. A decrease in cell viability, loss of the MMP and an increase in apoptosis rate induced by this synergy could be significantly attenuated by the ROS scavenger N-acetylcysteine and JNK inhibitor SP600125. Conclusion Our results suggested that the combination of AgNTs and GEM possessed broad-spectrum and potent synergistic anti-glioma activity, resulting from cell apoptosis mediated by a ROS-dependent mitochondrial pathway in which JNK might be involved.