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The effects of a COX‐2 inhibitor meloxicam on squamous cell carcinoma of the esophagus in vivo
Author(s) -
Liu JunFeng,
Zhang ShaoWei,
Jamieson Glyn G.,
Zhu GuiJun,
Wu TieCheng,
Zhu TieNian,
Shan BaoEn,
Drew Paul A.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23288
Subject(s) - meloxicam , apoptosis , in vivo , esophagus , western blot , medicine , cancer , esophageal cancer , prostaglandin e2 , cancer research , pathology , biology , biochemistry , microbiology and biotechnology , gene
Our previous study showed that aspirin induced apoptosis of esophageal cancer cells in vitro by inhibiting the pathway of NF‐kappaB downstream regulation of cyclooxygenase‐2. The purpose of this study was to determine if similar changes occurred in vivo in the tumors of patients with SCC of the esophagus who were given a preferential COX‐2 inhibitor, meloxicam. Fifty‐three patients who had an esophagectomy for SCC were allocated randomly to either a Treatment group ( n = 25) or a control group ( n = 28). Patients in the Treatment group were given 7.5 mg/day of meloxicam, for between 10 and 14 days before surgery. Patients in the control group did not take any type of NSAID during this time interval. Samples of the tumor taken from the resected specimens were collected. Proliferation and apoptosis were measured by flow cytometry. The concentration of 6‐keto‐prostaglandin F 1 α in cancer tissue was determined by radio‐immuno‐assay. Expression of COX‐2 mRNA was measured with RT‐PCR and COX‐2 protein levels with Western blot analysis. Nuclear NF‐kappaB and cytoplasmic IkappaB protein levels were determined by electrophoretic mobility shift assay and Western blot, respectively. There were significantly more apoptotic cells in the tumors of patients who were using meloxicam. It also decreased the levels of COX‐2 mRNA, COX‐2 protein and nuclear NF‐kappaB protein and increased the cytoplasmic IkappaB protein in the cancer. We conclude that meloxicam induces apoptosis in SCC of the esophagus in vivo by inhibiting the pathway of NF‐kappaB downstream regulation of COX‐2. © 2007 Wiley‐Liss, Inc.