Ann Surg. 2005 Dec;242(6):840-9, discussion 849-50.
Neoadjuvant selective COX-2 inhibition down-regulates important oncogenic pathways in patients with esophageal adenocarcinoma.
Tuynman JB, Buskens CJ, Kemper K, ten Kate FJ, Offerhaus GJ, Richel DJ, van Lanschot JJ.
Departments of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
To evaluate the effects of neoadjuvant therapy with the selective
cyclooxygenase-2 (COX-2) inhibitor celecoxib in vitro and in patients
with esophageal adenocarcinoma on COX-2 and MET expression.
BACKGROUND DATA: High COX-2 and/or MET expression levels are negative
prognostic factors for adenocarcinoma of the esophagus. Nonsteroidal
anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors exert
anticancer mechanisms as is evident from epidemiologic studies and from
experimental models for esophageal cancer. The mechanisms and the
significance of these findings in patients with adenocarcinoma of the
esophagus are unknown.
METHODS: Esophageal adenocarcinoma cell lines
were used to asses the effects in vitro. To study the clinical effects
12 patients with esophageal adenocarcinoma were included for
neoadjuvant treatment (4 weeks) with celecoxib at 400 mg twice daily.
Fifteen patients not receiving NSAIDs or celecoxib were included as a
control. Effects were evaluated using the MTT-cell viability test,
Western blot analysis, immunohistochemistry, and RT-PCR.
vitro celecoxib administration resulted in decreased cell viability,
increased apoptosis, and decreased COX-2 and MET expression levels. In
patients, neoadjuvant treatment with celecoxib significantly
down-regulated COX-2 and MET expression in the tumor when compared with
the nontreated control group and when compared with pretreatment
CONCLUSIONS: This is the first study to show in vitro and
in patients with esophageal adenocarcinoma that selective COX-2
inhibition down-regulates COX-2 and MET expression, both important
proteins involved in cancer progression and dissemination. Therefore,
(neo)adjuvant therapy with celecoxib might have clinical potential for
patients with esophageal adenocarcinoma.