氧化石墨烯-氯喹纳米复合物通过自噬调控诱导 A549 癌细胞发生坏死性死亡。
Graphene oxide-chloroquine nanoconjugate induce necroptotic death in A549 cancer cells through autophagy modulation.
机构信息
CSIR-National Physical Laboratory, Dr K. S. Krishnan Marg, New Delhi 110012, India.
Academy of Scientific & Innovative Research (AcSIR), Sector 19, Ghaziabad, UP 201002, India.
出版信息
Nanomedicine (Lond). 2018 Sep;13(18):2261-2282. doi: 10.2217/nnm-2018-0086. Epub 2018 Oct 4.
AIM
Chloroquine (Chl) has shown its potential in cancer therapy and graphene oxide (GO) exhibited excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate Chl to GO sheets and investigated the nonproliferation action on A549 cell lines along with cell signaling pathways.
MATERIALS & METHODS: Cellular toxicity, autophagic flux modulation and cell death mechanism induced by GO-Chl have been investigated on A549 cell lines.
RESULTS & CONCLUSION: GO-Chl induces accumulation of autophagosomes (monodansylcadaverine staining, green fluorescence protein-tagged LC3 plasmid and transmission electron microscopy observations) in A549 cells through the blockade of autophagic flux that serves as scaffold for necrosome assembling and activates necroptotic cell death. GO-Chl nanoconjugate could be used as an effective cancer therapeutic agent, by targeting the autophagy necroptosis axis.
目的
氯喹（Chl）在癌症治疗中显示出其潜力，氧化石墨烯（GO）表现出优异的肿瘤靶向能力、生物相容性和低毒性。我们致力于将 Chl 与 GO 片结合，并研究其对 A549 细胞系的非增殖作用以及细胞信号通路。
材料与方法
在 A549 细胞系上研究了 GO-Chl 引起的细胞毒性、自噬流调节和细胞死亡机制。
结果与结论
GO-Chl 通过阻断自噬流在 A549 细胞中诱导自噬体的积累（单丹磺酰尸胺染色、绿色荧光蛋白标记的 LC3 质粒和透射电子显微镜观察），自噬流作为坏死体组装的支架，并激活坏死性细胞死亡。GO-Chl 纳米复合物可以通过靶向自噬-坏死性细胞死亡轴，用作有效的癌症治疗剂。
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