Open Access

PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis

  • Authors:
    • Jie Wu
    • Sheng Xiao
    • Miaomiao Yuan
    • Qianyuan Li
    • Guangfen Xiao
    • Wei Wu
    • Yuexian Ouyang
    • Lihua Huang
    • Chenjiao Yao
  • View Affiliations

  • Published online on: November 6, 2018     https://doi.org/10.3892/mmr.2018.9628
  • Pages: 75-84
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.
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January-2019
Volume 19 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wu J, Xiao S, Yuan M, Li Q, Xiao G, Wu W, Ouyang Y, Huang L and Yao C: PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis. Mol Med Rep 19: 75-84, 2019
APA
Wu, J., Xiao, S., Yuan, M., Li, Q., Xiao, G., Wu, W. ... Yao, C. (2019). PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis. Molecular Medicine Reports, 19, 75-84. https://doi.org/10.3892/mmr.2018.9628
MLA
Wu, J., Xiao, S., Yuan, M., Li, Q., Xiao, G., Wu, W., Ouyang, Y., Huang, L., Yao, C."PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis". Molecular Medicine Reports 19.1 (2019): 75-84.
Chicago
Wu, J., Xiao, S., Yuan, M., Li, Q., Xiao, G., Wu, W., Ouyang, Y., Huang, L., Yao, C."PARP inhibitor re‑sensitizes Adriamycin resistant leukemia cells through DNA damage and apoptosis". Molecular Medicine Reports 19, no. 1 (2019): 75-84. https://doi.org/10.3892/mmr.2018.9628