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...

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Veröffentlicht in:Annals of the New York Academy of Sciences 2009-08, Vol.1171 (1), p.635-641
Hauptverfasser: Kim, Su-Hyeon, Kim, Su-Hyeong, Song, Yoo-Choel, Song, Yong-Sang
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Kim, Su-Hyeong
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Song, Yong-Sang
description 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 μmol/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 μmol/L celecoxib with 10 μmol/L cisplatin increased COX‐2 expression. However, the combination of 30 μmol/L celecoxib and 30 μmol/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 μmol/L celecoxib or 10 μmol/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.
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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 μmol/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 μmol/L celecoxib with 10 μmol/L cisplatin increased COX‐2 expression. However, the combination of 30 μmol/L celecoxib and 30 μmol/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 μmol/L celecoxib or 10 μmol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. 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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 μmol/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 μmol/L celecoxib with 10 μmol/L cisplatin increased COX‐2 expression. However, the combination of 30 μmol/L celecoxib and 30 μmol/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 μmol/L celecoxib or 10 μmol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. 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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 μmol/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 μmol/L celecoxib with 10 μmol/L cisplatin increased COX‐2 expression. However, the combination of 30 μmol/L celecoxib and 30 μmol/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 μmol/L celecoxib or 10 μmol/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.</abstract><cop>Malden, USA</cop><pub>Blackwell Publishing Inc</pub><pmid>19723114</pmid><doi>10.1111/j.1749-6632.2009.04888.x</doi><tpages>7</tpages></addata></record>
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subjects Anticancer properties
Antineoplastic Agents - pharmacology
Biotechnology
Blotting, Western
Cancer
Celecoxib
Cell Line, Tumor
Cell Proliferation - drug effects
cisplatin
Cisplatin - pharmacology
COX-2 inhibitors
cyclooxygenase
Cyclooxygenase 1 - metabolism
Cyclooxygenase 2 - metabolism
Cyclooxygenase Inhibitors - pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Effectiveness
Enzymes
Female
Humans
Inhibition
Piroxicam - pharmacology
Progressions
Prostaglandin-Endoperoxide Synthases - metabolism
Pyrazoles - pharmacology
Sulfonamides - pharmacology
vulvar cancer
Vulvar Neoplasms - metabolism
Vulvar Neoplasms - pathology
title Celecoxib Potentiates the Anticancer Effect of Cisplatin on Vulvar Cancer Cells Independently of Cyclooxygenase
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