Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, China.
Department of Biological Pharmaceutical, School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.
J Biochem Mol Toxicol. 2020 May;34(5):e22474. doi: 10.1002/jbt.22474. Epub 2020 Feb 11.
With the rapid development of nanotechnology, nanomaterials are now being used for cancer treatment. Although studies on the application of silver nanoparticles in cancer treatment are burgeoning, few studies have investigated the toxicology mechanisms of autophagy in cancer cells under exposure to sublethal silver nanoparticles. Here, we clarified the distinct mechanisms of silver nanoparticles for the regulation of autophagy in prostate cancer PC-3 cells under sublethal exposure. Silver nanoparticle treatment caused lysosome injury, including the decline of lysosomal membrane integrity, decrease of lysosomal quantity, and attenuation of lysosomal protease activity, which resulted in blockage of autophagic flux. In addition, sublethal silver nanoparticle exposure activated AMP-activated protein kinase/mammalian target of rapamycin-dependent signaling pathway to modulate autophagy, which resulted from silver nanoparticles-induced cell hypoxia and energy deficiency. Taken together, the results show that silver nanoparticles could regulate autophagy via lysosome injury and cell hypoxia in PC-3 cells under sublethal dose exposure. This study will provide an experimental basis for the cancer therapy of nanomaterials.
随着纳米技术的飞速发展，纳米材料现在被用于癌症治疗。虽然关于银纳米粒子在癌症治疗中的应用的研究正在蓬勃发展，但很少有研究探讨在亚致死剂量的银纳米粒子暴露下癌细胞自噬的毒理学机制。在这里，我们阐明了在亚致死暴露下，银纳米粒子在调节前列腺癌细胞 PC-3 中的自噬方面的不同机制。银纳米粒子处理导致溶酶体损伤，包括溶酶体膜完整性下降、溶酶体数量减少和溶酶体蛋白酶活性减弱，从而导致自噬流受阻。此外，亚致死银纳米粒子暴露激活了 AMP 激活的蛋白激酶/雷帕霉素哺乳动物靶蛋白依赖性信号通路来调节自噬，这是由于银纳米粒子诱导的细胞缺氧和能量缺乏所致。总之，这些结果表明，在亚致死剂量暴露下，银纳米粒子可以通过溶酶体损伤和细胞缺氧来调节 PC-3 细胞中的自噬。这项研究将为纳米材料的癌症治疗提供实验基础。
