Combination therapy with clopidogrel and 5-fluorouracil (5-FU) reduce the growth and metastasis of 4T1 tumors.

Abstract

<p>(A) Tumor weight on day 26 and kinetics of tumor growth. (B) Number of lung metastatic foci. (C) Expression of E- and N-cadherin in tumor tissue (left graph), E:N-cadherin ratio (middle) and representative blots (right). (D) Platelets’ morphological parameters, including platelet count, platelet distribution width (PDW), mean platelet volume (MPV), and plateletcrit (PCT). (E) ELISA measurements of plasma proteins corresponding to platelets activity: von Willebrant factor (vWF), thromboxane b2 (TXB2), transforming growth factor beta 1 (TGF-β1), P-selectin, and prostacyclin metabolite (6-keto-PGF1α). All graphs show values for individual animals with median line; the exception is panel D: mean with standard error of mean (SEM) and kinetics of tumor growth: mean with standard deviation (SD) is presented. N = 10 mice per group; some tests were performed on tissue or plasma from selected animals from each group (at least 3 in western blot tests; data for individual blots presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0188740#pone.0188740.s015" target="_blank">S1 Table</a>). All mice were euthanized on day 26. Statistical analysis: Kruskal–Wallis test for multiple comparisons; *<i>p</i><0.05. The values of selected morphological parameters of platelets in healthy BALB/c mice: platelet count: 245 ± 95 [×10<sup>3</sup>/μL]; MPV: 6.6 ± 0.3 [fL]; PDW: 47 ± 1 [fL]; PCT: 0.2 ± 0.06 [%]. The level of TGF-β1: 320 ± 449; P-selectin: 100 ± 10 in healthy BALB/c mice.</p

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