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首页> 美国卫生研究院文献>International Journal of Nanomedicine >Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy
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Combination of salinomycin and silver nanoparticles enhances apoptosis and autophagy in human ovarian cancer cells: an effective anticancer therapy

机译：沙利霉素和银纳米颗粒的组合可增强人卵巢癌细胞的凋亡和自噬：一种有效的抗癌治疗

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Ovarian cancer is one of the most important malignancies, and the origin, detection, and pathogenesis of epithelial ovarian cancer remain elusive. Although many cancer drugs have been developed to dramatically reduce the size of tumors, most cancers eventually relapse, posing a critical problem to overcome. Hence, it is necessary to identify possible alternative therapeutic approaches to reduce the mortality rate of this devastating disease. To identify alternative approaches, we first synthesized silver nanoparticles (AgNPs) using a novel bacterium called Bacillus clausii. The synthesized AgNPs were homogenous and spherical in shape, with an average size of 16–20 nm, which are known to cause cytotoxicity in various types of human cancer cells, whereas salinomycin (Sal) is able to kill cancer stem cells. Therefore, we selected both Sal and AgNPs to study their combined effect on apoptosis and autophagy in ovarian cancer cells. The cells treated with either Sal or AgNPs showed a dose-dependent effect with inhibitory concentration (IC)-50 values of 6.0 µM and 8 µg/mL for Sal and AgNPs, respectively. To determine the combination effect, we measured the IC25 values of both Sal and AgNPs (3.0 µM and 4 µg/mL), which showed a more dramatic inhibitory effect on cell viability and cell morphology than either Sal or AgNPs alone. The combination of Sal and AgNPs had more pronounced effect on cytotoxicity and expression of apoptotic genes and also significantly induced the accumulation of autophagolysosomes, which was associated with mitochondrial dysfunction and loss of cell viability. Our data show a strong synergistic interaction between Sal and AgNPs in tested cancer cells. The combination treatment increased the therapeutic potential and demonstrated the relevant targeted therapy for the treatment of ovarian cancer. Furthermore, we provide, for the first time, a mode of action for Sal and AgNPs in ovarian cancer cells: enhanced apoptosis and autophagy.
机译：卵巢癌是最重要的恶性肿瘤之一，上皮性卵巢癌的起源，检测和发病机制仍然难以捉摸。尽管已经开发出许多癌症药物来显着减小肿瘤的大小，但大多数癌症最终都会复发，这是需要克服的关键问题。因此，有必要确定可能的替代治疗方法以降低这种破坏性疾病的死亡率。为了确定替代方法，我们首先使用一种名为克劳氏芽孢杆菌的新型细菌合成了银纳米颗粒（AgNP）。合成的AgNPs均一且呈球形，平均大小为16-20 nm，已知会在各种类型的人类癌细胞中引起细胞毒性，而沙利霉素（Sal）能够杀死癌症干细胞。因此，我们选择了Sal和AgNPs来研究它们对卵巢癌细胞凋亡和自噬的联合作用。用Sal或AgNPs处理的细胞表现出剂量依赖性，Sal和AgNPs的抑制浓度（IC）-50值分别为6.0 µM和8 µg / mL。为了确定组合效果，我们测量了Sal和AgNP的IC25值（3.0 µM和4 µg / mL），与单独使用Sal或AgNP相比，它们对细胞活力和细胞形态的抑制作用更为显着。 Sal和AgNPs的组合对细胞毒性和凋亡基因的表达具有更明显的作用，并且还显着诱导自噬体的积累，这与线粒体功能障碍和细胞活力丧失有关。我们的数据显示，Sal和AgNPs在测试的癌细胞之间具有强大的协同作用。联合治疗增加了治疗潜力，并证明了针对卵巢癌的相关靶向治疗。此外，我们首次提供了卵巢癌细胞中Sal和AgNPs的作用方式：增强凋亡和自噬作用。

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