Poly(ADP-ribose) polymerase inhibition down-regulates expression of metastasis-related genes in CT26 colon carcinoma cells.

OBJECTIVES The current study was designed to test the hypothesis that inhibition of poly(ADP-ribose) polymerase in colorectal cancer mediates down-regulation of metastasis-related gene expression through the regulation of nuclear factor-kappaB (NF-kappaB) activity. METHODS Mouse colon carcinoma cells (CT26) were treated with and without the PARP inhibitor 5-aminoisoquinolin-1(2H)-one hydrochloride (5-AIQ). We investigated adhesion, migration and invasion of differently treated CT26 cells. In addition, the expression levels of PARP, NF-kappaB, integrin beta(1), MMP-9 and MMP-2 as well as the activities of NF-kappaB, MMP-9 and MMP-2 were determined by Western blot, electrophoretic mobility gel shift assay and zymography, respectively. RESULTS Inhibition ofPARP attenuated the adhesion of CT26 cells to the extracellular matrix and their migration and invasion through Matrigel. In addition, the results of Western blot showed that the expression levels of PARP, NF-kappaB, integrin beta(1), MMP-9 and MMP-2 were reduced in 5-AIQ-treated CT26 cells; the activities of NF-kappaB, MMP-9 and MMP-2 were also suppressed. CONCLUSIONS Inhibition of PARP down-regulates the expression of metastasis-related genes in mouse colon carcinoma cells. This could be, at least in part, through the regulation of NF-kappaB activity, but the precise mechanisms of action remain to be elucidated.