Plumbagin inhibits cell growth and potentiates apop-tosis in human gastric cancer cells -in vitro through the NF-KB 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 viab ity 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-KB- regulated gene products and TNF-（x-induced activation of p65, IKB（x, and IKK. The intracellular location of NF-KB p65 was detected using confocal microscopy. Results： Plumbagin （2.5-40 pmol/L） concentration-dependently reduced the viability of the GC cells. The ICso value of plumbagin in SGC-7901, MKN-28, and AGS cells was 19.12, 13.64, and 10.12 pmol/L, respectively. The compound （5-20 pmol/L） concentration- dependently induced apoptosis of SGC-7901 cells, and potentiated the sensitivity of SGC-7901 celts to chemotherapeutic agents TNF- （xand cisplatin. The compound （10 pmol/L） downregulated the expression of NF-KB-regulated gene products, including lAP1, XIAP, Bcl- 2, Bcl-xL, tumor factor （TF）, and VEGF. In addition to inhibition of NF-KB p65 nuclear translocation, the compound also suppressed TNF-α-induced phosphorylation of p65 and IKK, and the degradation of IKB（X. Conclusion： Plumbagin inhibits cell growth and potentiates apoptosis in human GC cells through the NF-KB pathway.