Sodium salicylate inhibits proliferation and induces G1 cell cycle arrest in human pancreatic cancer cell lines

The mutations most common in pancreatic cancer decrease the ability to cont rol G1 to S cell circle progression and cellular proliferation. In colorect al cancer cells, nonsteroidal anti-inflammatory drugs inhibit proliferation and induce cell cycle arrest. We examined whether sodium salicylate, an as pirin metabolite, could inhibit proliferation in human pancreatic cancer ce ll lines (BxPC3 and Panc-1). Quiescent cells were treated with medium conta ining 100% fetal calf serum. with or without salicylate. Cellular prolifera tion was measured by MTT assay and bromodeoxyuridine incorporation. The fra ctions of cells in G0/G1, S, and G2/M phases of the cell cycle were quantit ated by fluorescence-activated cell sorting. Results were compared between groups by two-tailed t test. Cyclin D1 expression was determined by Western blot analysis and prostaglandin E-2 expression by enzyme-linked immunosorb ent assay. Scrum starved cells failed to proliferate, with most arrested in the G1 phase. Salicylate significantly inhibited serum-induced progression from G1 to S phase, cellular proliferation, and the expression of cyclin D 1. The concentrations at which 50% of serum-induced proliferation was inhib ited were 1.2 mmol/L (Panc-1) and 1.7 mmol/L. (BsPC3). The antiproliferativ e effect of sodium salicylate was not explained by inhibition of prostaglan din E-2 production. This study provides further evidence in a noncolorectal cancer model for the antineoplastic effects of nonsteroidal anti-inflammat ory drugs.