COX-2 expression and effects of COX-2 inhibition in colorectal carcinomas and their liver metastases.
Nonsteroidal anti-inflammatory drugs are known to reduce the risk and mortality from colorectal carcinoma by inhibiting cyclo-oxygenases (COX). COX-2 expression was investigated immunohistologically in 57 patients with colorectal carcinomas and in the corresponding liver metastases using tissue microarray analysis. Ex vivo COX-2 inhibition with assessment of apoptosis was performed using precision-cut tissue slices of three human liver metastases. Following stimulation with different concentrations of the selective COX-2 inhibitor meloxicam, apoptosis was assessed immunohistochemically after 6 h and 12 h. All primary carcinomas and 56 out of the 57 liver metastases showed various degrees of cytoplasmatic COX-2 expression being with a reduction and in the liver metastases. There was a time- and concentration-dependent change in the number of apoptotic cells in tissue slices, however, this was without statistical significance. COX-2 is constantly involved in the carcinogenesis and metastatic process of colorectal cancer. The antineoplastic effect of COX-2 inhibition may be based on different pathways, including changes in sensitivity to apoptosis.
Kasper
Hans-Udo
HU
Institut für Pathologie, Medical Center am Clemenshospital, Düesberweg 128, D-48153 Münster/Wfl., Germany. e-mail@patho-muenster.de
Konze
Elisabeth
E
Dienes
Hans Peter
HP
Stippel
Dirk Ludger
DL
Schirmacher
Peter
P
Kern
Michael
M
D000236:Adenoma / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000502:physiology; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D000077239:Meloxicam; D008875:Middle Aged; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D046888:Tissue Array Analysis
D052246:Cyclooxygenase 2 Inhibitors; D013843:Thiazines; D013844:Thiazoles; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000077239:Meloxicam