Effect of NF-κB Constitutive Activation on Proliferation and Apoptosis of Gastric Cancer Cell Lines

Abstract

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 AM^TM 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 < 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-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.

Plumbagin inhibits cell growth and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway

“…The NF-κB proteins, and other proteins associated with the NF-κB pathway, have been linked to cellular transformation, proliferation, apoptosis suppression, and angiogenesis [14] . In GC cells, NF-κB was shown to be constitutively activated [15] , and the activation of NF-κB has been touted as a prognostic parameter in gastric carcinoma [16] . Thus, agents that suppress NF-κB activation have great potential to be effective in the prevention and treatment of GC.…”

Oral administration of Pyrrolidine Dithiocarbamate (PDTC) inhibits VEGF expression, tumor angiogenesis, and growth of breast cancer in female mice

“…14,15 Of these, PDTC is the most potent NFκB inhibitor. 16 PDTC has been shown to inhibit NFκB activation for suppressing tumor growth in colorectal cancer, 17 and for inducing pro-apoptotic and anti-proliferative effects in prostate cancer, 18 ovarian carcinoma cells, 19 breast cancer cells, 20 T-cell leukemia, 21 lymphoma, 22 gastric cancer cells 23 and renal cell carcinoma. 24 The expression of genes, such as vascular endothelial growth factor (VEGF), is also stimulated by NFκB, which is involved in angiogenesis.…”

Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats

“…Recent studies have shown that PDTC stimulates apoptosis via suppressing activation of NF-nB in various cancer cells (e.g. acute myelogenous leukemia, prostate cancer, and gastric cancer) [9][10][11]. In contrast, PDTC has also been shown to reduce endothelial cell apoptosis induced by hypoxia [12].…”