| Duan Qiuhua,Feng Yue,Hu Lijun,et al.Effect of poly adenosine diphosphate ribose polymerase inhibitor on the radiosensitivity of breast cancer cells and underlying mechanism[J].Chinese Journal of Radiological Medicine and Protection,2023,43(12):945-953 |
| Effect of poly adenosine diphosphate ribose polymerase inhibitor on the radiosensitivity of breast cancer cells and underlying mechanism |
| Received:July 06, 2023 |
| DOI：10.3760/cma.j.cn112271-20230706-00228 |
| KeyWords:PARP inhibitors Breast cancer Radiosentivity DNA damage repair Apoptosis |
| FundProject:上海市卫健委卫生行业临床研究专项项目(202340160);常州市卫健委重大科技项目(ZD202017);常州市"十四五"高层次卫生人才培养工程拔尖人才(2022CZBJ070);上海中医药大学科技发展基金(23KFL105) |
| Author Name | Affiliation | E-mail | | Duan Qiuhua | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Feng Yue | Department of Radiation Oncology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | | | Hu Lijun | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Wang Jianlin | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Zeng Hongwei | Department of Radiation Oncology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | | | Sun Fei | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Meng Qinghong | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Zhou Mengyun | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China | | | Yu Jingping | Department of Radiation Oncology, Changzhou Second People's Hospital Affiliated to Nanjing Medical University, Changzhou 213003, China
Department of Radiation Oncology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China | yujingping700420@sina.com |
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| Abstract:: |
| Objective To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SERD0 and SERDq value increased. Compared with control group, the percentages of cells in G2/M phase were increased (tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G0/G1 phase were decreased (tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased (tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation (t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group (t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased (tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased (t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased (tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased (t=2.90, P<0.05) in the combination group.Conclusions PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair. |
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