Antiproliferative and apoptotic effects of rofecoxib on esophageal cancer in vitro(1).
BACKGROUND
The incidence of Barrett's adenocarcinoma has increased dramatically in the United States, whereas squamous cell carcinoma of the esophagus remains a worldwide problem. Cyclooxygenase (COX)-2 may play an important role in gastrointestinal carcinogenesis and is overexpressed in both Barrett's metaplasia and adenocarcinoma. We hypothesized that a selective and commercially available COX-2 inhibitor, rofecoxib (Vioxx), would inhibit growth of Barrett's adenocarcinoma and squamous cell carcinoma of the esophagus by apoptotic pathways. Additional comparison studies were performed with commercially available COX-2 and COX-1 inhibitors.


METHODS
Two esophageal adenocarcinoma cell lines (SEG-1 and BIC) and two esophageal squamous cell cancer lines (KYSE 150 and KYSE 410) were treated with rofecoxib at doses ranging from 8.0 to 125 microg/well. NS-398 (a COX-2 antagonist) and Catechin (a COX-1 antagonist) were also used at doses of 50 and 100 microM. Esophageal cell viability was measured by MTT at 24 and 72 h. Apoptosis was evaluated after 18 h of incubation with rofecoxib, NS398, and Catechin by flow cytometry via annexin V assay.


RESULTS
Rofecoxib, NS-398, and Catechin treatments all resulted in significant antiproliferative effects in both adenocarcinoma and squamous cell carcinoma of the esophagus in vitro. Substantial increases in apoptotic activity were also found in all cell lines.


CONCLUSIONS
Our findings suggest that COX-2 and COX-1 inhibition has potential to become an effective treatment for both histological variants of esophageal cancer. Further in vivo and human studies are warranted to evaluate the safety and clinical utility of these agents in patients with all cancers of the esophagus.
Vona-Davis
Linda
L
Department of Surgery, Robert C. Byrd Health Science Center, West Virginia University, Morgantown, West Virginia, USA.
Riggs
Dale R
DR
Jackson
Barbara J
BJ
McFadden
David W
DW
D000230:Adenocarcinoma; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000166:cytology / Q000187:drug effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004938:Esophageal Neoplasms; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007783:Lactones / Q000494:pharmacology*; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D009578:Nitrobenzenes; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases