Celecoxib potentiates the anticancer effect of cisplatin on vulvar cancer cells independently of cyclooxygenase.
Cyclooxygenase-2 (COX-2) has been found to be associated with the development and progression of various cancers. Our previous study showed a high expression rate of COX-2 in paraffin-embedded tissue specimens from patients with vulvar cancer. In this study, we evaluated the efficacy of celecoxib, a selective COX-2 inhibitor, as a chemosensitizing agent with cisplatin in vulvar cancer cells A431 and SW962. COX-2 was expressed in both A431 and SW962 vulvar cancer cell lines. COX-1 was expressed in A431 but not in SW962. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay showed that treatment with 30 micromol/L celecoxib had no effect on cell growth in A431 cells for 72 h. However, combined treatment with celecoxib and cisplatin induced a significant reduction in cell growth compared to single treatment with cisplatin. Interestingly, single treatment with celecoxib or cisplatin and combined treatment of 10 micromol/L celecoxib with 10 micromol/L cisplatin increased COX-2 expression. However, the combination of 30 micromol/L celecoxib and 30 micromol/L cisplatin reduced COX-2 expression to the control state. Inhibition of cell growth by celecoxib alone and in combination with cisplatin was independent of the expression level of COX-2 induced by these agents. While treatment with 10 micromol/L celecoxib or 10 micromol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. Taken together, celecoxib could be used as a chemosensitizing agent in vulva cancer cells; the anticancer activity of celecoxib seemed to be independent of COX.
Kim
Su-Hyeon
SH
Cancer Research Institute, World Class University, Seoul National University College of Medicine, Seoul, Korea.
Kim
Su-Hyeong
SH
Song
Yoo-Choel
YC
Song
Yong-Sang
YS
D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006801:Humans; D010894:Piroxicam / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014846:Vulvar Neoplasms / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D010894:Piroxicam; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D002945:Cisplatin