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、25.0和50.0μg/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及50μg/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4nm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。
Objective:To explore the toxicity and close-response relationship of 4-nm gold nanoparticles (AuNPs) on human lung adenocarcinoma cell line A549. Methods:Sodium citrate solution (the control group) and three concentrations (12.5,25.0 and 50.0 μg/ml) of 4-nm AuNPs solution were respectively added to the culture medium of A549 cells for 48 h incubation. The morphology and internalization of AuNPs in 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:TEM showed that the shape and size of AuNPs particles were homogeneous and mainly distributed in small vesicles,cytoplasm,lysosomes or the perinuclear region in A549 cells. Compared to the control group, 4-nm AuNPs significantly reduced the cell viability in a doseresponse relationship (P 〈 0.05). The results of flow cytometry showed that AuNPs with higher concentration (25 and 50 μg/ml) significantly increased the apoptosis of A549 cells (P 〈 0.05),while no significant difference in cell cycle. Conclusion:AuNPs with size of 4 nm can significantly reduce cell viability and promote apoptosis in a dose-response relationship in A549, which provides a new strategy for the treatment of lung cancer.