Liu Min, Zhao Yunxue, Zhang Xiumei
Department of Pharmacology, School of Medicine, Shandong University, Jinan, Shandong, PR China.
PLoS One. 2015 Mar 19;10(3):e0118870. doi: 10.1371/journal.pone.0118870. eCollection 2015.
Gold nanoparticles (GNPs) have shown promising medical applications in cancer treatment involved in the regulation of intracellular redox balance. Previously, we have reported that GNPs can trigger apoptosis and necrosis in human lung cancer cells (A549) when L-buthionine-sulfoximine (BSO) was used to decrease the expression of intracellular glutathione (GSH). Herein, we investigated the cytotoxicity of GNPs toward lung cancer cells under the glutamate cysteine ligase catalytic subunit (GCLC) was silenced by siRNA. Our results showed that GNPs cause apoptosis and necrosis in cells transfected with GCLC siRNA by elevating intracellular reactive oxygen species (ROS). These findings demonstrated that the regulation of glutathione synthesis by GCLC siRNA in A549 cells can initiate the gold nanoparticles-induced cytotoxicity.
金纳米颗粒（GNPs）在涉及调节细胞内氧化还原平衡的癌症治疗中已显示出有前景的医学应用。此前，我们曾报道，当使用L-丁硫氨酸-亚砜亚胺（BSO）来降低细胞内谷胱甘肽（GSH）的表达时，GNPs可引发人肺癌细胞（A549）凋亡和坏死。在此，我们研究了在谷氨酸半胱氨酸连接酶催化亚基（GCLC）被小干扰RNA（siRNA）沉默的情况下，GNPs对肺癌细胞的细胞毒性。我们的结果表明，GNPs通过提高细胞内活性氧（ROS）水平，导致转染了GCLC siRNA的细胞发生凋亡和坏死。这些发现表明，在A549细胞中，GCLC siRNA对谷胱甘肽合成的调节可引发金纳米颗粒诱导的细胞毒性。
