Cyclooxygenase inhibitors decrease the growth and induce regression of human esophageal adenocarcinoma xenografts in nude mice

Abstract

Abstract. Cyclooxygenase (COX) inhibition has been shown to prevent the development of esophageal adenocarcinoma (EAC). However, the potential of this approach for treatment of established cancer has been poorly investigated. Our objective was to determine whether non-selective or selective inhibition of the COX pathway affects the growth of esophageal adenocarcinoma xenografts in nude mice. A human esophageal adenocarcinoma xenograft model was established by subcutaneous inoculation of OE33 cells in nude mice. Small tumor slices harvested from four OE33 xenografts were implanted in the flanks of new mice that were randomized to different treatments (6 animals per group): indomethacin (3 mg/kg/day), parecoxib (0.11 and 0.22 mg/ kg/day) or a selective prostaglandin E 2 receptor antagonist (AH-23848B, 1 mg/kg/day). For each treatment, a control group of 6 animals (vehicle) carrying xenografts from the same OE33 tumor was included. Tumor growth was measured twice a week. After 8 weeks mice were euthanized. Tumors were assessed by histological analysis, mRNA expression of COX isoenzymes, PGE 2 receptors and PGE 2 content. All OE33 tumors were poorly differentiated esophageal adenocarcinomas. Tumors expressed COX-2, EP 1 , EP 2 and EP 4 receptor mRNA. Treatment with parecoxib, higher dose or indomethacin significantly inhibited tumor growth. Furthermore, indomethacin induced tumor regression (74 vs 582% in control animals; p<0.01). However, AH-23848B or parecoxib low dose failed to affect tumor growth significantly. PGE 2 content in tumors was significantly decreased by high-dose parecoxib and indomethacin. Indomethacin and parecoxib inhibit the growth of human esophageal adenocarcinoma xenografts in nude mice, which suggests a potential role for NSAIDs or selective COX-2 inhibitors for EAC chemotherapy.

Non-Steroidal Anti-inflammatory Drugs Decrease E2F1 Expression and Inhibit Cell Growth in Ovarian Cancer Cells

“…Data is represented as means ± standard errors. The concentrations of diclofenac and indomethacin used for this study are similar to others that have been previously shown to be effective and well-tolerated in mice [4], [10], [11], [18].…”

“…In addition, in vitro and animal studies have shown that NSAIDs can decrease the initiation and/or progression of several cancers [4], [5], [6]. For example, the NSAID indomethacin inhibited the growth of chemically-induced colon cancers in rats [7], [8].…”

Ibuprofen results in alterations of human fetal testis development

“…These genes are expressed in a population of mitotic fetal germ cells named gonocytes. NSAIDs have been shown to promote cell cycle arrest and apoptosis thereby decreasing the initiation and/or progression of various cancers (colorectal, bladder, skin, esophageal adenocarcinoma, ovarian)63646566. Whether ibuprofen effects occur by similar mechanisms remains to be established.…”

Acetylsalicylic Acid Exhibits Antitumor Effects in Esophageal Adenocarcinoma Cells In Vitro and In Vivo

“…The OE33 xenograft EAC model was established as previously described [14]. Briefly, OE-33 cells in logarithmic phase of growth (10 7 cells) were injected subcutaneously using a 27-gauge needle in the flank of a mouse.…”