[Effects of selective cyclooxygenase-2 inhibitor NS-398 on 5-fluorouracil chemotherapy and progression of colon cells: an experimental study].
OBJECTIVE
To investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitor NS-398 on 5-fluorouracil (5-Fu) chemotherapy and on the progression of colon cells.


METHODS
Colon cancer cells of HT-29 and SW480 lines were cultured. Selective COX-2 inhibitor NS-398, 5-Fu, or NS-398 combining with 5-Fu were added into the cultures to be co-cultured for 24, 48, and 72 hours respectively. RT-PCR and ELISA analysis were performed to detect the level of COX-2 mRNA expression and prostaglandin 2 (PGE2) concentration in the cells of both HT-29 and SW480 lines. The proliferation and apoptosis of the two cell lines were observed with MTT assay and flow cytometry.


RESULTS
Expression of COX-2 mRNA were negative in SW480 line and positive in HT-29 line. Compared with SW480 line, the HT-29 line showed an obvious decline of PGE2 concentration following NS-398 treatment. Both NS-398 and 5-Fu inhibited the cells' proliferation and induced apoptosis in a dose-dependent manner, and a more significant inhibition was found when the cells were co-treated with NS-398 and 5-Fu. Although, there was no significant difference between these in inducing apoptosis.


CONCLUSIONS
Selective COX-2 inhibitor NS-398 can inhibit the proliferation of colon cancer cells and induce apoptosis thereof. The mechanism of NS-398 against colon cancer may be independent upon the expression levels of COX-2 mRNA and PGE2 of colon cancer. NS-398 may be a subsidiary drug in 5-Fu chemotherapy in treating colon cancer.
Zhang
You-cheng
YC
Department of Surgery, Peking University People's Hospital, Beijing 100044, China.
Wang
Shan
S
Zhang
Hui
H
Ye
Ying-jiang
YJ
Liang
Bin
B
Cui
Zhi-rong
ZR
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D009578:Nitrobenzenes / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011453:Prostaglandins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D009578:Nitrobenzenes; D011453:Prostaglandins; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D005472:Fluorouracil