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

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.