Abstract:

Objective   To investigate the effects of poly(ADP-ribose)polymerase-1(PARP-1) inhibitor PJ34 on the growth activity and cisplatin resistance of cisplatin-resistant ovarian cancer C13* cells in vitro. Methods   MTT assay and flow cytometry were used to determine influences of PJ34 on cisplatin sensitivity, apoptosis and the cell cycle of C13* cells. The expression level of PARP-1 in C13* cells was determined using immunofluorescence microscopy  and Western blot, and changes induced by PJ34 treatment were investigated. Results   The inhibitory ratio and  cisplatin sensitivity of C13* cells were significantly increased with increases of concentrations of platinum (Pt) and PJ34 (P<0.05). The apoptosis ratio of C13* cells was significantly increased with the increase of the concentration of PJ34(P<0.05). The proportion of cells in the G0/Gl phase in the high concentration PJ34-treated group was larger than that in the low concentration PJ34-treated group. PJ34 down-regulated the PARP-1 expression in C13* cells，which was remarkably decreased when Pt and PJ34 co-treated(P<0.01). Conclusion   PJ34 remarkably down-regulates the PARP-1 protein expression, inhibits proliferation activity, promotes apoptosis, and increases sensitivity to cisplatin of C13* cells. Hopefully, PJ34 could effectively reverse resistance of C13*cells to cisplatin.

Key words: Poly(ADP-ribose)polymerase-1； PJ34； Ovarian cancer； Drug resistance