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.
Conclusion: 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.