Phenotypic Characteristics Of Cell Death In Human Gastric Cancer Cells Induced By "Dextran-Magnetic Layered Complex Hydroxide-Fluorouracil" Drug Delivery System

Objective The purpose of the paper is to study the mechanism in oncosis of MGC-803induced by“dextran-magnetic layered double hydroxide-fluorouracil”?DMF?drug delivery system and 5-Fu,respectively.Methods The morphology of cell death was detected by transmission electron microscopy?TEM?.Oncosis and its phenotypic difference were researched using CCK-8,immunofluorescence,the detection ATP,mitochondrial membrane potenti-al?MMP?,reactive oxygen species?ROS?and Ca²⁺,western blotting and acid phosphatase?ACP?in DMF-induced MGC-803/SGC-7901.Results DMF can induc apoptosis and oncosis in MGC-803/SGC-7901.DMF had more obvious effect in suppressing proliferation compared with 5-Fu for cancer cells.The IC50 was263.1?g·mL^-1,1876?g·mL^-1 in MGC-803 cells;327.0?g·mL^-1 and 2261.8?g·mL^-1 in SGC-7901,respectively.DMF can induce mitochondrial dysfunction,causing Ca²⁺increase,ATP decrease and mitochondrial membrane potential loss,but does not reactive oxygen accumulation.DMF can cause endoplasmic reticulum stress?ERS?effect,including that there is a potential of cascade reaction of Caspase-7,Caspase-12,Caspase-9,Caspase-3 and PARP.DMF can activate the pro-porimin receptor,however,the effect was not significant compared with 5-Fu on the level of perforin,calpain and porimin levels.DMF showed a stronger degradation on nuclear membrane and PARP in the Caspase-8,Caspase-6,Caspase-9,Caspase-3 and Lamin-A cascade reaction.DMF can change the level of ACP in a short period of time.Conclusion DMF can cause a lot of vacuolization of organelles and trigger rapid depletion of ATP,which is consistent with the phenotype of oncosis.Endogenous mitochondrial apoptosis isn't the main cause of cell swelling.DMF can induce strong ERS effect,there may be some signaling pathways related with ERS during the process of oncosis.The calpain system isn't a key factor for structural damage in oncosis induced by DMF.DMF can induce the caspases cascade reactions similar to apoptosis,but there is a more stronger damage on nuclear membrane and PARP.