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

Abstract

The mutations most common in pancreatic cancer decrease the ability to control G1 to S cell cycle progression and cellular proliferation. In colorectal cancer cells, nonsteroidal anti-inflammatory drugs inhibit proliferation and induce cell cycle arrest. We examined whether sodium salicylate, an aspirin metabolite, could inhibit proliferation in human pancreatic cancer cell lines (BxPC3 and Panc-1). Quiescent cells were treated with medium containing 10% fetal calf serum, with or without salicylate. Cellular proliferation was measured by MTT assay and bromodeoxyuridine incorporation. The fractions of cells in G0/G1, S, and G2/M phases of the cell cycle were quantitated 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 E2 expression by enzyme-linked immunosorbent assay. Serum-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 D1. The concentrations at which 50% of serum-induced proliferation was inhibited were 1.2 mmol/L (Panc-1) and 1.7 mmol/L (BxPC3). The antiproliferative effect of sodium salicylate was not explained by inhibition of prostaglandin E2 production. This study provides further evidence in a noncolorectal cancer model for the antineoplastic effects of nonsteroidal anti-inflammatory drugs.