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

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Journal of Gastrointestinal Surgery

Abstract

The mutations most common in pancreatic cancer decrease the ability to control Gl 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. Cydin Dl 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 Gl phase. Salicylate significantly inhibited serum-induced progression from Gl to S phase, cellular proliferation, and the expression of cyclin Dl. 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 annproliferative 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.

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Authors and Affiliations

  1. Department of Surgery, University of Massachusetts Medical School, Worcester, Mass.

    Theodore P. McDade M.D., Frank J. Vittimberga Jr. M.D., Andrew J. Duffy M.D. & Mark P. Callery M.D., FA.C.S. (Associate Professor of Surgery and Cell Biology)

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  1. Richard A. Perugini M.D.
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  2. Theodore P. McDade M.D.
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  3. Frank J. Vittimberga Jr. M.D.
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Perugini, R.A., McDade, T.P., Vittimberga, F.J. et al. Sodium salicylate inhibits proliferation and induces Gl cell cycle arrest in human pancreatic cancer cell lines. J Gastrointest Surg 4, 24–33 (2000). https://doi.org/10.1016/S1091-255X(00)80029-3

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