Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea.
Molecules. 2018 Aug 15;23(8):2046. doi: 10.3390/molecules23082046.
Although many treatment strategies have been reported for lung disease, the mechanism of combination therapy using silver nanoparticles (AgNPs) and histone deacetylases inhibitors (HDACi) remains unclear. Therefore, innovative treatment strategies are essential for addressing the therapeutic challenges of this highly aggressive lung cancer. AgNPs and HDACi seem to be the best candidates for anticancer therapy because of their anti-proliferative effect in a variety of cancer cells. First, we synthesized AgNPs using wogonin as a reducing and stabilizing agent, following which the synthesized AgNPs were characterized by various analytical techniques. The synthesized AgNPs exhibited dose- and size-dependent toxicity towards A549 cells. Interestingly, the combination of AgNPs and MS-275 significantly induces apoptosis, which was accompanied by an increased level of reactive oxygen species (ROS); leakage of lactate dehydrogenase (LDH); secretion of TNFα; dysfunction of mitochondria; accumulation autophagosomes; caspase 9/3 activation; up and down regulation of pro-apoptotic genes and anti-apoptotic genes, respectively; and eventually, induced DNA-fragmentation. Our findings suggest that AgNPs and MS-275 induce cell death in A549 lung cells via the mitochondrial-mediated intrinsic apoptotic pathway. Finally, our data show that the combination of AgNPs and MS-275 is a promising new approach for the treatment of lung cancer and our findings contribute to understanding the potential roles of AgNPs and MS-275 in pulmonary disease. However, further study is warranted to potentiate the use of this combination therapy in cancer therapy trials.
虽然已经报道了许多用于肺部疾病的治疗策略，但联合使用银纳米粒子（AgNPs）和组蛋白去乙酰化酶抑制剂（HDACi）的组合疗法的机制仍不清楚。因此，针对这种高度侵袭性肺癌，创新的治疗策略至关重要。AgNPs 和 HDACi 似乎是抗癌治疗的最佳候选者，因为它们在各种癌细胞中具有抗增殖作用。首先，我们使用白杨素作为还原剂和稳定剂合成了 AgNPs，然后通过各种分析技术对合成的 AgNPs 进行了表征。合成的 AgNPs 对 A549 细胞表现出剂量和尺寸依赖性的毒性。有趣的是，AgNPs 和 MS-275 的组合显着诱导凋亡，伴随着活性氧（ROS）水平的增加；乳酸脱氢酶（LDH）漏出；TNFα 的分泌；线粒体功能障碍；自噬体积累；caspase 9/3 激活；促凋亡基因和抗凋亡基因的上调和下调；最终导致 DNA 片段化。我们的研究结果表明，AgNPs 和 MS-275 通过线粒体介导的内在凋亡途径诱导 A549 肺细胞死亡。最后，我们的数据表明，AgNPs 和 MS-275 的组合是治疗肺癌的一种很有前途的新方法，我们的研究结果有助于了解 AgNPs 和 MS-275 在肺部疾病中的潜在作用。然而，需要进一步的研究来增强这种联合治疗在癌症治疗试验中的应用。
