, Volume 15, Issue 3, pp 323-328

Effect of Poly (ADP-ribose) Polymerase-1 Inhibition on the Proliferation of Murine Colon Carcinoma CT26 Cells

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Abstract

To investigate effect of poly (ADP-ribose) polymerase inhibition on the proliferation of CT26 cells in vitro and the mechanism of this effect. CT26 cells were treated with a range of concentrations of 5-Aminoisoquinolin-1-one (PARP inhibitor) in vitro. MTT assays and flow cytometry were used to determine the proliferation and cell cycle distribution, respectively, of the cells. The expression of PARP-1 was investigated by Western blot. The binding of Nuclear Factor-κB to DNA was detected by electrophoretic mobility shift assay. The proliferation of CT26 cells was significantly inhibited by 5-AIQ induced PARP inhibition in a dose-dependent manner. Proliferation was inhibited by 17.5% at 100 μM 5-AIQ, by 27.6% at 500 μM 5-AIQ and by 39.9% at 1000 μM (P < 0.05). After treatment with 5-AIQ, the proportion of cells in G0/Gl phases increased and the proportion of cells in S phase decreased. The expression of PARP-1 was attenuated in 5-AIQ-treated CT26 cells (P < 0.05) and the binding of NF-κB to DNA binding was similarly diminished (P < 0.05). These results suggest that PARP inhibition reduced the proliferation of CT26 cells in vitro and influences the cell cycle. This inhibition is mediated by inhibiting PARP-1, which then diminishes the activity of NF-κB.

Grants support

This work was supported in part by grant from the National Nature Science Foundation of China (NSFC: 30870946) and from Nature Science Foundation Project of Chongqing (CSTC: 2006BB5288)