检索历史 清除

摘要Background:Fuzheng Kang'ai decoction(FZKA)has been widely used to treat NSCLC patients in China for decades,showing definite curative effects in clinic.Recently,we've found that FZKA induces cell ferroptosis,another type of programmed cell death(PCD),which is totally different from cell apoptosis.Therefore,in the present study,we aim to discover the exact mechanism by which FZKA induces NSCLC cell ferroptosis,which is rarely studied in Traditional Chinese Medicine(TCM).Methods:Cell counting kit-8 assay and EdU proliferation assay were performed to detect the cell growth inhibition.Non-small-cell lung cancer(NSCLC)cell ferroptosis triggered by FZKA treatment were observed via lipid peroxidation assay,Fe2+ Ions assay,and mitochondrial ultrastructure by transmission electron microscopy.Then the ratio of GSH/GSSG was done to measure the alteration of oxidative stress.Western blot and qRT-PCR were carried out to detect the expression of SLC7A11 and SLC3A2,especially GPX4 at protein and mRNA level,respectively.Results:First of all,the experiment confirmed the inhibition effect of FZKA in NSCLC cell growth.We then,for the first time,found that FZKA induces NSCLC cell ferroptosis evidently,by increasing lipid peroxidation and cellular Fe2+ Ions.Meanwhile,characteristic morphological changes of NSCLC cell ferroptosis was observed under transmission electron microscopy.Mechanistically,glutathione peroxidase 4(GPX4),as a key inhibititor of lipid peroxidation,was greatly suppressed by FZKA treatment both at protein and mRNA levels.Furthermore,system xc-(SLC7A11 and SLC3A2)were suppressed and a decreased GSH/GSSG ratio was observed at the same time by treating with FZKA.Conclusion:Our findings conclude that GPX4 plays a crucial role in FZKA-induced NSCLC cell ferroptosis,providing a novel molecular mechanism by which FZKA in treating NSCLC.