Study on the Function of NAG-1 in Hepatocellular and Gastric Carcinoma Cells

ABSTRACT

BACKGROUND: Nonsteroidal anti-inflammatory drug activated gene (NAG-1) has proapoptotic activities in the colon and also in gastric cancer cells that lack any endogenous COX-2 expression. Recent studies have suggested that the proa- poptotic activity of NAG-1 is cell type specific. I investigated the cell proliferation, invasiveness and apoptosis in Hep3B cells and SNU719 cells by determining the different expression levels of NAG-1. In addition, I examined the gene profile in the Hep3B cells that have a stable expression of NAG-1. METHODS: SNU719 cells and several clones of Hep3B cells with a stable expression of NAG-1 were used. I reduced the expression level of NAG-1 via the RNAi method. An Agilent Human 22k microarray was used for studying the gene profile in Hep3B cells that had a stable expression of NAG-1. RESULTS: The expression level of NAG-1 did not influence apoptosis, cell proliferation and invasiveness in Hep3B cells. There was no correlation between the reduction of the endogenous NAG-1 expression and cell proliferation, including invasiveness, in the SNU719 cells. However, a knocked-down NAG-1 expression protected against apoptosis in the SNU719 cells. The microarray analysis results showed that 0.25% (58/22,575) of the genes were induced or repressed more than three fold in the Hep3B cells that had a stable expression of NAG-1. CONCLUSIONS: Proapoptotic activity of NAG-1 is found in gastric cancer cells, but not in hepatocellular cancer cells.