Abstracts
1999 Digestive Disease Week

# 3473 SODIUM SALICYLATE DECREASES CYCLIN D1 EXPRESSION AND INDUCES G1 CELL CYCLE ARREST IN HUMAN PANCREATIC CANCER CELLS
R A Perugini, M P Callery, T P McDade, F J Vittimberga Jr., Univ of MA Med Sch, Worcester, MA

Mutations common in pancreatic cancer (i.e. K-ras, p53, p16) decrease the ability to control G1 to S cell cycle progression and cellular proliferation. In some cell lines, p38 mitogen activated protein kinase (p38-MAPK) activation decreases the expression of cyclin D1, a protein required to drive cells through G1 into S phase. We examined whether sodium salicylate (NaSal), which activates p38-MAPK, could induce cell cycle arrest and inhibit proliferation in a human pancreatic cancer cell line. Methods: BxPC-3 human pancreatic cancer cells were serum starved for 60 hours. Next, cells were repleted with media containing 10% fetal calf serum (FCS) alone or combined with NaSal at 0.5 or 5 mM and cells were incubated. Cellular proliferation was measured by MTT assay and by cell count (Trypan Blue exclusion). The fractions of cells in G0/G1, S, and G2/M phases of the cell cycle were quantitated by FACS analysis using the Modfit LT program (Verity). Results were compared between groups by two-tailed t-test (*p<0.05). Cyclin D1 expression was determined by Western blot. Results: Serum starved BxPC-3 cells failed to proliferate, with most (66%) arrested in G1. Additon of 10% FCS caused progression into S phase (Tab. 1), followed by proliferation (Fig. 1). This was associated with expression of cyclin D1 (Fig. 2). NaSal (5 mM) significantly inhibited serum-induced progression from G1 to S phase, the associated cellular proliferation, and the expression of cyclin D1. Conclusions: By decreasing cyclin D1 expression and inducting G1 cell cycle arrest, NaSal inhibits FCS-induced proliferation of human pancreatic cancer cells in vitro. This study provides further evidence in a non-colorectal cancer model for the cancer chemopreventive effects of NaSal.

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