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자료유형
학술저널
저자정보
저널정보
대한암학회 Cancer Research and Treatment Cancer Research and Treatment 제46권 제1호
발행연도
2014.1
수록면
81 - 92 (12page)

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PurposeCelecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of severaltypes of human cancer cells. The purpose of this study was to investigate whethercelecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells,and to identify the signal pathway by which celecoxib mediates apoptosis. Materials and MethodsOVCAR-3 cells were exposed to paclitaxel (20 μM) in the absence or presence ofcelecoxib (10 μM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosiswas evaluated using Annexin-V/7-aminoactinomycin D staining and a cellularDNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavageof poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-κB (NF-κB) and vascular endothelial growth factor (VEGF)and Akt activation were assessed using reverse transcriptase-polymerase chainreaction and western blotting. ResultsCelecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxibsignificantly increased paclitaxel-induced apoptosis of OVCAR-3 cells. Pretreatmentwith celecoxib also increased activation of caspase-9, -3 and cleaved PARP followingpaclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination withpaclitaxel resulted in downregulation of NF-κB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt. ConclusionOVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib throughdownregulation of NF-κB and Akt activation, suggesting that celecoxib may worksynergistically with paclitaxel to inhibit different targets and ultimately produceanticancer effects. Combining celecoxib with paclitaxel may prove beneficial in theclinical treatment of ovarian cancer.

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