BibTeX
@MISC{_background:we,
author = {},
title = {Background: We previously found that S100P, a member of},
year = {}
}
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Abstract
the S100 protein family, is expressed in more than 90 % of pancreatic tumors and is associated with tumor growth and invasion. In the current study, we investigated the ability of the antiallergy drug, cromolyn, to block S100P function. Methods: Interactions between cromolyn and S100P were investigated using a drug affi nity column and by examining cromolyn’s effects on coimmunoprecipitation of S100P and receptor for advanced glycation end-products (RAGE). The effects of cromolyn on cell growth, invasion, and nuclear factor- κ B (NF κ B) activity of pancreatic cancer cells with (BxPC-3 and MPanc-96) and without (Panc-1) endogenous S100P were investigated by cell proliferation assay, by cell invasion assay, and by luciferase reporter gene assay, respec-tively. The effects of cromolyn on tumor growth in vivo were investigated in three orthotopic models (n = 20 mice per model) by administration of cromolyn (5 mg/kg body weight, daily) with and without gemcitabine (125 mg/kg body weight, biweekly), the drug currently used to treat pancreatic cancer. Tumor growth was assayed by reporter gene expression. All statistical tests were two-sided. Results: S100P was retained on a cromolyn affi nity column. Cromolyn blocked the coim-munoprecipitation of S100P and RAGE. In vitro, cromolyn (100 μ M) inhibited S100P-stimulated Panc-1 cell proliferation (S100P, mean = 0.93 U, versus S100P + cromolyn, mean = 0.56 U, difference = 0.37 U; 95 % confi dence interval [CI] = 0.24 to 0.49 U; P =.001, n = 3), invasion (S100P, mean = 58.0%, versus S100P + cromolyn, mean = 9.4%, difference = 48.6%; 95 % CI = 38.8 % to 58.8%; P <.001, n = 3), and NF κ B activity (S100P, mean = 14 460, versus S100P + cromolyn, mean =
Keyphrases
versus s100p cromolyn tumor growth advanced glycation end-products cell growth pancreatic cancer pancreatic cancer cell reporter gene expression antiallergy drug luciferase reporter gene s100p function cromolyn effect statistical test cromolyn affi nity column confi dence interval ci current study endogenous s100p s100 protein family drug affi nity column pancreatic tumor orthotopic model mg kg body cell proliferation assay nuclear factor nf activity mg kg body weight cell invasion assay s100p-stimulated panc-1 cell proliferation
