BackgroundTriple-negative breast cancer(TNBC)is relatively common in women and is associated with a poor prognosis after surgery and adjuvant chemotherapy.Currently,the mechanism underlying the relationship between propofol and breast cancer is controversial and limited to cell apoptosis.Moreover,there are only a few studies on the effect of propofol on the chemotherapeutic sensitivity of TNBC cells.Therefore,this study explored whether propofol and its commonly used clinical formulations affect the proliferation and chemotherapeutic effects on TNBC cells by regulating cell ferroptosis.MethodsWe selected MDA-MB-231 cells,which is a kind of TNBC cell lines,treated with propofol,propofol injectable emulsion(PIE)and fospropofol disodium,alone or combined with doxorubicin or paclitaxel to conduct this study.The cell viability,apoptosis,intracellular reactive oxygen species(ROS)accumulation,ferroptosis-related morphological changes,intracellular Fe2+ levels,and the expression and localization of ferroptosis—related proteins(p53,SLC7A11 GPX4,FSP1,Ubiquinone,Ubiquinol)were investigated using CCK-8 kit,flow cytometry,DCFDA/H2DCFDA-cellular ROS assay kit,transmission electron microscopy,FerroOrange iron assay,western blot,and multiplex immunohistochemistry(mIHC).ResultsWe found that propofol significantly inhibited MDA-MB-231 cell proliferation,and all three propofol formulations augmented the anti-tumor effects of doxorubicin and paclitaxel.The results from the ROS assay,transmission electron microscopy,intracellular Fe2+ assay,western blot,and mIHC revealed that propofol not only induced apoptosis but also triggered ferroptosis-related changes,including morphological changes of mitochondria,increased intracellular ROS levels,and intracellular iron accumulation in MDA-MB-231 cells.The ferroptosis-related p53-SLC7A11-GPX4 pathway was also altered under different treatment propofol,doxorubicin,or paclitaxel regimens.ConclusionPropofol showed anti-proliferation effects on TNBC cells and could be a potential adjuvant to enhance the chemotherapeutic sensitivity of TNBC cells partly by promoting cell ferroptosis.BackgroundIschemia/reperfusion(I/R)injury is a common complication after hepatic surgery,which may associated with poor prognosis,prolonged length of stay and increased cost.It is reported that ferroptosis is related with hepatic I/R injury.Inhibition of ferroptosis may become a new strategy to protect patients against hepatic I/R injury.Propofol injectable emulsion(PIE)is one of the most commonly used intravenous anesthetics in clinical practice.According to the previous research and our own results,we speculated that exogenous emulsion in PIE may have protective effect through ferroptosis resistance.In this study,we used hepatocyte I/R injury model to explore whether PIE could alleviate I/R injury by inhibiting ferroptosis of hepatocytes,hoping to provide a new strategy for perioperative organ protection.MethodsNormal rat hepatocyte line IAR20 and hypoxia/reoxygenation(H/R)model were used to simulate hepatic I/R injury,and the effects of PIE,propofol,and emulsion on the IAR20 cell line after I/R injury(H/R injury)were compared.Our study mainly had three parts:1.the effects of PIE on IAR20 cell line after I/R injury;2.the effects of PIE on the ferroptosis of IAR20 cell line;3.whether the effects of PIE on IAR20 cell line after I/R injury associated with ferroptosis.The cell viability,ferroptosis-related morphological changes,mitochondrial membrane potential,intracellular reactive oxygen species(ROS)accumulation and intracellular Fe2+ levels were investigated using CCK-8 kit,transmission electron microscopy,JC-1 kit,DCFDA/H2DCFDA-cellular ROS assay kit and FerroOrange iron assay kit.ResultsOur results suggest that,first,PIE and emulsion could improve the IAR20 cell viability after H/R injury,compared with propofol.Second,the analyses from the cell viability,ferroptosis-related morphological changes,mitochondrial membrane potential,intracellular ROS and Fe2+ assay revealed that PIE and emulsion could alleviate the ferroptosis of IAR20 cell line induced by Erastin,a famous activator of ferroptosis,but propofol did not show these effects.Third,also through the results of CCK-8 kit,transmission electron microscopy,JC-1 kit,DCFDA/H2DCFDA-cellular ROS assay kit and FerroOrange iron assay kit,we found that PIE and emulsion protected IAR20 cell line against H/R injury,consistent with the inhibitor of ferroptosis,Ferrostatin-1,while propofol did not.ConclusionPIE could protect hepatocytes against I/R injury through inhibiting ferroptosis.This protective effect was mainly attributed to the exogenous emulsion in PIE,but not to its propofol component. |