Interferon-α resistance can be reversed by inhibition of IFN-α-induced COX-2 expression potentially via STAT1 activation in A549 cells

The current study demonstrates that COX-2 expression is positively regulated by IFN-α, which is mediated by activation of STAT1 in A549 cells. The IFN-α-induced COX-2 expression and STAT1 activation were markedly inhibited by the addition of curcumin to the IFN-α-pretreated cells. While IFN-α or COX-2 inhibitors alone did not result in growth inhibition of A549 cells, the combination of IFN-α 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-α possibly via STAT1 activation in the A549 human non-small cell lung cancer cell line, which may partly account for its IFN-α resistance. The addition of curcumin or celecoxib to the IFN-α-pretreated A549 cells altered the IFN-α sensitivity of cell growth inhibition.