| Zhao Wei,Yin Xue,Zhu Xiaodong,Liang Xia,Qu Song,Li Ye,Li Ling.Regulatory mechanisms of the radiosensitive effect of PARP-1 inhibitor on breast cancer cells with BRCA mutation[J].Chinese Journal of Radiological Medicine and Protection,2016,36(3):168-172 |
| Regulatory mechanisms of the radiosensitive effect of PARP-1 inhibitor on breast cancer cells with BRCA mutation |
| Received:July 19, 2015 |
| DOI：10.3760/cma.j.issn.0254-5098.2016.03.002 |
| KeyWords:PARP-1 BRCA mutation Radiosensitivity Breast Cancer DNA break repair |
| FundProject:国家自然科学基金(81260346);广西自然科学基金(2013GXNSFBA019199);广西医疗卫生科研课题(32012346);广西重点实验室专项经费(GK2014-ZZ09);广西高等学校重大科研经费(201101ZD004) |
| Author Name | Affiliation | E-mail | | Zhao Wei | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Yin Xue | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Zhu Xiaodong | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Liang Xia | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Qu Song | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Li Ye | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | | | Li Ling | Department of Radiation Oncology, Cancer Hospital of Guangxi Medical University, Nanning 530021, China | lilingmoon99@163.com |
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| 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. |
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