Abstract
The current study demonstrates that COX-2 expression is positively regulated by IFN-alpha, which is mediated by activation of STAT1 in A549 cells. The IFN-alpha-induced COX-2 expression and STAT1 activation were markedly inhibited by the addition of curcumin to the IFN-alpha-pretreated cells. While IFN-alpha or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-alpha and celecoxib or curcumin resulted in a significant growth inhibition of A549 cells, which was associated with down-regulation of CDK2, 4, and 6 and up-regulation of p27. We demonstrate that the expression of COX-2 was induced by IFN-alpha possibly via STAT1 activation in the A549 human non-small cell lung cancer cell line, which may partly account for its IFN-alpha resistance. The addition of curcumin or celecoxib to the IFN-alpha-pretreated A549 cells altered the IFN-alpha sensitivity of cell growth inhibition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Carcinoma, Non-Small-Cell Lung / drug therapy
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Carcinoma, Non-Small-Cell Lung / enzymology
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Carcinoma, Non-Small-Cell Lung / genetics
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Curcumin / pharmacology
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Cyclooxygenase 2 / biosynthesis*
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Cyclooxygenase 2 / genetics
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DNA, Neoplasm / metabolism
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Drug Interactions
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Drug Resistance, Neoplasm
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Enzyme Induction / drug effects
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Humans
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Interferon-alpha / antagonists & inhibitors*
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Interferon-alpha / pharmacology*
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Lung Neoplasms / drug therapy
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Lung Neoplasms / enzymology
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Lung Neoplasms / genetics
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Membrane Proteins / biosynthesis*
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Membrane Proteins / genetics
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Phosphorylation / drug effects
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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STAT1 Transcription Factor / biosynthesis
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STAT1 Transcription Factor / genetics
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STAT1 Transcription Factor / metabolism*
Substances
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DNA, Neoplasm
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Interferon-alpha
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Membrane Proteins
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RNA, Messenger
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STAT1 Transcription Factor
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Cyclooxygenase 2
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PTGS2 protein, human
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Curcumin