Poly(ADP-ribose) polymerase inhibition down-regulates expression of metastasis-related genes in CT26 colon carcinoma cells.
OBJECTIVE
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.
Li
Ming
M
Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
Threadgill
Michael D
MD
Wang
Yalan
Y
Cai
Li
L
Lin
Xiao
X
D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016328:NF-kappa B; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9