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 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.
Perugini
R A
RA
Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts 01655-0333, USA.
McDade
T P
TP
Vittimberga
F J
FJ
Duffy
A J
AJ
Callery
M P
MP
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D019938:Cyclin D1 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D016196:S Phase / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019938:Cyclin D1; D001241:Aspirin