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

Objective: To observe whether there is constitutive activation of nuclear transcription factor kappa B ( NF- kappa B) and its effect on proliferation and apoptosis of human gastric cancer cell lines. Methods: Nuclear/ cytoplasmic protein expression of NF- kappa B was analyzed by Western blot in four different gastric cancer cell lines. Trans AM(TM) NF- kappa B p65 Kit was used for detecting the difference of p65 activity. The effect of PDTC ( pyrrolidine dithiocarbamate), a specific inhibitor of NF- kappa B 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- kappa B 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 SGC7901 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- kappa B and the cell proliferation were significantly inhibited in experimental group treated by PDTC, compared with control groups ( p < 0.01). An increased apoptotic rate and a decreased proliferating activity were observed after the gastric cancer cells were exposed to PDTC for 24 h. Conclusions: These results suggested that the constitutive activation and the protein expression of NF- kappa B are different in gastric cancer cell lines. PDTC can inhibit NF- kappa B activity and cell proliferation, which related to an increased cell apoptosis. The results disclosed that NF-kappa B could be a potential therapeutic target for solid tumor therapy. Copyright (C) 2005 S. Karger AG, Basel.