Growth inhibitory effect of celecoxib and rofecoxib on human colorectal carcinoma cell lines.
BACKGROUND
Epidemiological studies have revealed a protective effect of NSAIDs, which principally target cyclooxygenase (COX)-1 and COX-2, on the development of colorectal cancer. Increased expression of COX-2 was shown in colorectal adenocarcinoma. However, some effects were shown to be COX-independent. Here, we compared two selective COX-2 inhibitors for their effect on the growth of colorectal tumour cells in vitro.


METHODS
Fifteen tumour cell lines were characterized for COX-1 and COX-2 expression by Western blot and RT-PCR. The effect of celecoxib and rofecoxib on their growth was assessed by staining of DNA with crystal violet.


RESULTS
COX-2 expression varied among cell lines, whereas COX-1 was always expressed. Rofecoxib displayed a limited dose-related effect on cell proliferation, whereas celecoxib strongly inhibited cell growth at high concentrations. Both effects appeared COX-2-independent.


CONCLUSIONS
Rofecoxib, which is devoid of apoptotic effect at high concentration but efficient at pharmacological concentrations, revealed a potential new mechanism of action of NSAIDs towards colorectal cancer.
Buecher
Bruno
B
Centre de Recherche en Nutrition Humaine de Nantes, INSERM U539, CHU Hôtel-Dieu, 44035 Nantes, France.
Bouancheau
Delphine
D
Broquet
Alexis
A
Bezieau
Stéphane
S
Denis
Marc G
MG
Bonnet
Christian
C
Heymann
Marie-Françoise
MF
Jarry
Anne
A
Galmiche
Jean-Paul
JP
Blottière
Hervé M
HM
D018938:Caco-2 Cells; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D008565:Membrane Proteins; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D011720:Pyrazoles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*; D013450:Sulfones / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D008565:Membrane Proteins; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib