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

J Gastrointest Surg. 2000 Jan-Feb;4(1):24-32, discussion 32-3. doi: 10.1016/s1091-255x(00)80029-3.


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.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Aspirin / pharmacology*
  • Blotting, Western
  • Cell Division / drug effects
  • Cell Separation
  • Cyclin D1 / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • G1 Phase / drug effects
  • Humans
  • Mutation
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • S Phase / drug effects
  • Tumor Cells, Cultured / drug effects


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclin D1
  • Aspirin