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《中国药理学报：英文版》
>Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway
Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway
Aim:To investigate the effects and underlying mechanisms of plumbagin,a naphthoquinone derived from medicinal plant Plumbago zeylanica,on human gastric cancer (GC) cells.Methods:Human gastric cancer cell lines SGC-7901,MKN-28,and AGS were used.The cell viability was examined using CCK-8 viability assay.Cell proliferation rate was determined using both clonogenic assay and EdU incorporation assay.Apoptosis was detected via Annexin V/propidium iodide double-labeled flow cytometry.Western blotting was used to assess the expression of both NF-κBregulated gene products and TNF-α-induced activation of p65,IKBα,and IKK.The intracellular location of NF-κB p65 was detected using confocal microscopy.Results:Plumbagin (2.5-40 μmol/L) concentration-dependently reduced the viability of the GC cells.The IC50 value of plumbagin in SGC-7901,MKN-28,and AGS cells was 19.12,13.64,and 10.12 μmol/L,respectively.The compound (5-20 μmol/L) concentrationdependently induced apoptosis of SGC-7901 cells,and potentiated the sensitivity of SGC-7901 cells to chemotherapeutic agents TNFαand cisplatin.The compound (10 μmol/L) downregulated the expression of NF-κB-regulated gene products,including lAP1,XlAP,Bcl2,Bcl-xL,tumor factor (TF),and VEGF.In addition to inhibition of NF-κB p65 nuclear translocation,the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK,and the degradation of IκBα.Conclusion:Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-κB pathway.
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