金纳米颗粒对人肺腺癌细胞株A549的毒性效应-南京医科大学.DOC

金纳米颗粒对人肺腺癌细胞株A549的毒性效应 吴玉呈，刘正霞，郭志睿，周萍，鲁翔* (南京医科大学第二附属医院老年科，江苏 南京 210029) 摘要 目的: 探讨直径4 nm的金颗粒对人肺腺癌细胞株A549的毒性以及浓度-效应关系。方法: 在A549细胞培养液中，分别加入柠檬酸钠溶液(对照组)以及浓度分别为12.5 ug/ml、25 ug/ml和50 ug/ml的直径4 nm的金颗粒溶液，孵育48 h。采用透射电子显微镜(TEM)鉴定金纳米颗粒并观察其在细胞内的分布情况；采用细胞增殖和毒性试剂盒检测细胞活力；采用流式细胞术检测A549的细胞周期和凋亡。结果: TEM显示，金纳米颗粒大小及形态均一，主要分布于A549细胞的微小囊泡、胞浆、溶酶体以及细胞核周围。与对照组相比，4 nm金颗粒能显著降低细胞活力(P 0.05)，且具有浓度-效应关系。流式细胞检测结果显示，较高浓度(25 ug/ml及50 ug/ml) 4 nm金颗粒处理后，A549细胞凋亡比例显著增加(P 0.05)，但细胞周期未见显著性差异。结论: 直径4 nm的金颗粒能显著降低A549的细胞活力，促进A549凋亡，且具有浓度-效应关系，为肺癌的治疗提供了一种新思路。 关键词 金纳米颗粒；A549；毒性；浓度-效应关系Toxicity of gold nanoparticles in human lung adenocarcinoma cell line A549 Wu Yucheng, Liu Zhengxia, Guo Zhirui, Zhou Ping, Lu Xiang* (Department of Geriatrics, the Second Affiliated Hospital, Nanjing Medical University, Jiangsu, Nanjing, 210029) AbstractObjective: To explore the toxicity and dose-response relationship of 4 nm sized gold nanoparticles (AuNPs) on human lung adenocarcinoma cell line A549. Methods: Sodium citrate solution (control group) and three concentrations (12.5 ug/ml, 25 ug/ml, 50 ug/ml) of 4 nm sized AuNPs solution were respectively added to the culture medium of A549 cells followed by 48 h incubation. The morphology of AuNPs and the internalization into A549 cells were observed by transmission electron microscopy (TEM); cell viability of A549 was detected using cell proliferation and toxicity kit; cell cycle and apoptosis of A549 were analyzed by flow cytometry. Results: This study showed that the shape and size of particles were homogeneous and AuNPs mainly distributed in small vesicles, cytoplasm, lysosomes or the perinuclear region in A549. Compared to the control group, 4 nm AuNPs significantly reduced the cell viability in a dose-response relationship (P 0.05). AuNPs with higher concentration (25 ug/ml and 50 ug/ml) significantly increased apoptosis of A549 cells (P 0.05), while no significant difference in cell cycle. Conclusions: AuNPs with size of 4 nm can significantly reduce cell viability a