Effect of cyclooxygenase-2 antisense oligodeoxyribonucleotides in A-549 lung cancer cells.
BACKGROUND
Cyclooxygenase (COX)-2 is overexpressed in several tumor entities and seems to play a key role in carcinogenesis. This makes it a potential target in cancer therapy.


METHODS
Twelve phosphorothioate-modified antisense oligonucleotides (asODNs) against six targets of COX-2 mRNA were transfected to A-549 lung carcinoma cells. COX-2 mRNA and protein levels were determined by quantitative RT-PCR and flow cytometry, respectively. Cell growth was assessed by measuring Alamar Blue reduction.


RESULTS
The tested asODNs exhibited a range of activities. The most potent asODN reduced uninduced COX-2 mRNA to 66% and protein level to 75%, respectively. While this asODN did not influence cell growth, a 15% growth reduction was observed after transfection of another asODN which suppressed COX-2 mRNA to 71% and protein level to 84%.


CONCLUSIONS
The use of asODNs directed against COX-2 mRNA is a promising approach to inhibit COX-2 expression in tumor cells.
Windhövel
Ute
U
Department of Surgery/Surgical Research Laboratory, University Clinic of Schleswig-Holstein, Campus Lübeck, 23562 Lübeck, Germany. windhoev@uni-luebeck.de
Haasper
Carl
C
Duchrow
Michael
M
Bruch
Hans-Peter
HP
Broll
Rainer
R
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics* / Q000628:therapy*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000628:therapy*; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases