Regulatory mechanisms of the radiosensitive effect of PARP-1 inhibitor on breast cancer cells with BRCA mutation / 中华放射医学与防护杂志

ABSTRACT

Objective To investigate the radiosensitivity effects of poly ADP-ribose polymerase-1 (PARP-1) inhibitor 3-amion benzamide (3-AB) on the BRCA non-mutant and BRCA mutant breast cancer cells,and to explore the regulatory mechanism of PARP-1 and BRCA in radiation-induced DNA damage repair.Methods MDA-MB-436 cells and MDA-MB-231 cells were divided into four groups respectively as the control (CTRL),ionizing radiation alone (IR),3-AB alone (3-AB),and ionizing radiation combined with 3-AB(IR + 3-AB)group.γ-H2AX foci were detected by immunofluorescence assay.The radiosensitivity of breast cancer cells was evaluated by clonogenic survival assay.The percentage of apoptotic cells was assessed by flow cytometry.Results Compared with MDA-MB-231 cells,MDA-MB-436 cells had a higher radiosensitivity and produced more γ-H2AX foci(t =4.57,P ＜ 0.05),which was further increased by 3-AB.The DNA damage of MDA-MB-436 cells in the IR + 3-AB group was the most remarkable (t =3.26,P ＜ 0.05).Flow cytometry showed that the cells in the IR + 3-AB group had the highest rate of apoptosis (t=3.81,P ＜ 0.05),and the apoptosis rate of MDA-MB-436 cells was significantly higher than MDA-MB-231 cells (t =2.96,P ＜ 0.05).Conclusions The radiosensetivity of BRCA mutant cells MDA-MB-436 is significantly higher than that of non-BRCA mutant cells MDA-MB-231.Inhibition of PARP-1 can further increase the apoptosis and radiosensitivity of BRCA-mutant cells by further blocking the repair of DNA single-strand break induced by ionizing radiation.