[Effect of PARP-1 inhibitor 4-amino-1 ,8-naphthalimide on the on the sensitivity of adriamycin].
ABSTRACT To explore the effect of inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) on the sensitivity of cells to adriamycin (ADM).
Mouse embryonic fibroblasts (MEFs) were divided into two groups according to whether they were treated with 4-amino-1,8-naphthalimide (4-AN) or not. And then the differences of cell viability and genotoxicity between the 4-AN treatment group and the non-treated group were compared after exposure to ADM.
The half-inhibitory concentrations of ADM (IC50) in the 4-AN treatment group was significantly lower than the non-treated group (P < 0.05). At 0.025-0.2 microg/ml concentration of ADM, the cell viability of the treatment group was significantly lower than that of the non-treated group (P < 0.05). Moreover, the population doubling time and the colony formation rate were significant longer or higher (P < 0.05) at 0.05-0.2 microg/ml concentration of ADM. Results from the comet assay and micronucleus assay showed that the doses of ADM increased, the comet rate, tail length, Olive tail moment, frequency of micronucleated cells and frequency of micronucleus formation of the both groups increased. At 0.02-1 microg/ml concentration of ADM, the comet rate, tail length, Olive tail moment of the treatment group were significant higher than those of controls (P < 0.05), and at 0.01-0.2 microg/ml concentration of ADM, both the frequency of micronucleated cells and the frequency of micronucleus formation were significantly increased (P < 0.05).
Inhibition of PARP-1 can significantly increase the sensitivity of cells to adriamycin, and DNA damage and repair may be a potential mechanism for this effect.