Effect of NF-kappaB constitutive activation on proliferation and apoptosis of gastric cancer cell lines.

Objective: To observe whether there is constitutive activation of nuclear transcription factor ĸB (NF-ĸB) and its effect on proliferation and apoptosis of human gastric cancer cell lines. Methods: Nuclear/cytoplasmic protein expression of NF-ĸB was analyzed by Western blot in four different gastric cancer cell lines. Trans AMTM NF-ĸB p65 Kit was used for detecting the difference of p65 activity. The effect of PDTC (pyrrolidine dithiocarbamate), a specific inhibitor of NF-ĸB on the proliferation of gastric cancer cells, was measured by MTT (3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide) method. The apoptotic rates of AGS and SGC-7901 gastric cancer cell lines were measured with flow cytometer (FCM) after treatment by PDTC. Results: The constitutive activations of NF-ĸB were identified in four gastric cancer cell lines. The expression of activated subunit of p50 was lower in AGS cell line, and higher in MKN28, MKN45 and SGC-7901 cell lines. The expression of activated subunit of p65 was lower in MKN28 and MKN45 cell lines, and higher in AGS and SGC-7901 cell lines. Both the activity of NF-ĸB and the cell proliferation were significantly inhibited in experimental group treated by PDTC, compared with control groups (p Conclusions: These results suggested that the constitutive activation and the protein expression of NF-ĸB are different in gastric cancer cell lines. PDTC can inhibit NF-ĸB activity and cell proliferation, which related to an increased cell apoptosis. The results disclosed that NF-ĸB could be a potential therapeutic target for solid tumor therapy.