The Effect Of PARP Inhibition On The Invasion Of Murine Colon Carcinoma CT26 Cell Lines And Its Mechanism

Objective: The aim is to study the effect of poly(ADP-ribose) polymerase (PARP) inhibitor on the invasion of murine colon carcinoma CT26 cell lines in vitro,and its mechanism.Methods: CT26 cell lines were treated with or without PARP inhibitor 5-aminoisoquinolinone (5-AIQ) in vitro.The effects of 5-AIQ on the cell adhesion ,migration and invasion of CT26 were observed by cell- matrix adhesion assay, cell migration assay and matrigel invasion assay, respectively. The expressions of Integrinβ1, MMP-2 and MMP-9 of CT26 cells with or without 5-AIQ were investigated by Western Blot and the activities of MMP-2 and MMP-9 were detected by zymography.Results: 1. The result of cell-matrix adhesion assay showed that A values of 5-AIQ-treated groups were significantly reduced, when compared with untreated group (P<0.01). Meanwhile, comparing with untreated group, the migration and invasion potential of CT26 were both reduced by 5-AIQ treatment (P<0.01).2. The expressions of Integrinβ1, MMP-2 and MMP-9 of 5-AIQ-treated group were all significantly lower than the 5-AIQ-untreated group in western blot assay (P value were P<0.01, P<0.01, P<0.05, respectively). Interestingly, the activities of MMP-2 and MMP-9 were also attenuated in 5-AIQ-treated group comparing with 5-AIQ-untreated group (P value were P<0.05, P<0.01, respectively).Conclusion:1. The data suggest that PARP inhibitor 5-AIQ could reduce the cell-matrix adhesion, migration and invasion in CT26 cells. PARP inhibition might have a contribution for tumor invasion in some degree.2. 5-AIQ reduced the expressions of Integrinβ1, MMP-2 and MMP-9, and the activities of MMP-2 and MMP-9, which suggested that PARP inhibition suppressed the invasion-relative factors Integrinβ1, MMP-2 and MMP-9, then effected the metastasis of CT26 cells.