TY - JOUR AB - Resistance to Adriamycin (ADR) is an increasing problem in the treatment of leukemia and the development of novel therapeutic strategies is becoming increasingly important. Olaparib is a poly (adenosine diphosphate‑ribose) polymerase (PARP) 1 inhibitor, which has promising antitumor activity in patients with metastatic breast cancer and germline BRCA mutations. Previously published studies have indicated that Olaparib is able to overcome drug resistance in cancer; however, its underlying mechanism of action is yet to be elucidated. The aim of the present study was to explore the mechanism underlying re‑sensitization. Annexin V‑propidium iodide staining indicated that the percentage of apoptotic ADR resistant cells was markedly increased and the cell cycle was blocked at the G2/M‑phase following treatment with ADR combined with Olaparib, when compared with the control group. The alkaline comet assay demonstrated that ADR combined with Olaparib significantly upregulated the induction of the DNA damage response in ADR‑resistant cells. Western blot analysis revealed that the protein expression of γ‑H2A histone family member X, cleaved PARP, caspase 3 and cleaved caspase 3 was markedly enhanced, while the cell cycle‑associated protein cyclin B1 was downregulated in K562/ADR cells following treatment with a combination of ADR and Olaparib. Similar synergistic cytotoxicity was observed in blood mononuclear cells, which were isolated from patients with chemotherapy‑resistant leukemia. As Olaparib is available for clinical use, the results of the present study provide a rationale for the development of Olaparib combinational therapies for cases of ADR resistant leukemia. AD - Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China Center for Medical Experiments, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China AU - Wu,Jie AU - Xiao,Sheng AU - Yuan,Miaomiao AU - Li,Qianyuan AU - Xiao,Guangfen AU - Wu,Wei AU - Ouyang,Yuexian AU - Huang,Lihua AU - Yao,Chenjiao DA - 2019/01/01 DO - 10.3892/mmr.2018.9628 EP - 84 IS - 1 JO - Mol Med Rep KW - Olaparib drug resistance leukemia apoptosis Adriamycin PY - 2019 SN - 1791-2997 1791-3004 SP - 75 ST - PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis T2 - Molecular Medicine Reports TI - PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis UR - https://doi.org/10.3892/mmr.2018.9628 VL - 19 ER -