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Background.FRAP-p70s6K signaling regulates mitogenic responses to growth factors in eukaryotic cells. Constitutive p70s6K activation occurs in some human malignancies and may contribute to dysregulated cell growth. We examined whether inhibition of this pathway affects mitogen-induced proliferation and cell cycle progression of human pancreatic cancer cells in vitro.

Background.Genetic mutations found in pancreatic cancer (K-ras,p16, p53) lead to inappropriate cellular proliferation. Mitogens stimulate proliferation via the phosphatidylinositol 3-kinase (PI3K)- and/or the p44/42-mitogen-activated protein kinase [p44/42-MAPK or extracellular signal-regulated kinase (ERK)] signaling pathways. We examined whether inhibition of either PI3K or ERK could limit proliferation in human pancreatic cancer.

Introduction.Tumor necrosis factor (TNF-α)-induced apoptosis is limited by its coactivation of nuclear factor kappa B (NF-κB)-dependent anti-apoptotic genes. Sodium salicylate (NaSal) inhibits NF-κB activation by limiting phosphorylation and degradation of its bound inhibitor protein, IκB-α. We examined whether NaSal enhances TNF-α-induced apoptosis in cultured human pancreatic cancer cell lines.

Introduction.Transcriptional activation of the TNF-α gene in LPS-stimulated macrophages is dependent upon nuclear factor kappa-B (NF-κB) activity. Salicylates may interfere with NF-κB activity through a MAPK (mitogen-activated protein kinase)-dependent process. These studies investigate the effects of sodium salicylate (NaSal) on TNF-α production and MAPK activation in macrophages.