Open Access

KD025, an anti‑adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2‑overexpressing leukemia cells

  • Authors:
    • Wen Jing
    • Xuerong Zhang
    • Ruixia Chen
    • Xijiu Ye
    • Mao Zhou
    • Weixing Li
    • Wenchan Yan
    • Xiuxiu Xuyun
    • Jun Peng
  • View Affiliations

  • Published online on: September 30, 2020     https://doi.org/10.3892/ol.2020.12172
  • Article Number: 309
  • Copyright: © Jing et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Most patients with advanced leukemia eventually die from multidrug resistance (MDR). Chemotherapy‑resistant leukemia cells may lead to treatment failure and disease relapse. Overexpression of ATP‑binding cassette subfamily G member 2 (ABCG2) leads to MDR, which serves as a potential biomarker and target of therapeutic intervention for leukemia cells. Targeting ABCG2 is a potential strategy for selective therapy and eradicate MDR cells, thus improving malignant leukemia treatment. KD025 (SLx‑2119) is a novel Rho‑associated protein kinase 2‑selective inhibitor, which has been shown to inhibit adipogenesis in human adipose‑derived stem cells and restore impaired immune homeostasis in autoimmunity therapy. The present study demonstrated that KD025 improved the efficacy of antineoplastic drugs in ABCG2‑overexpressing leukemia cells and primary leukemia blast cells derived from patients with leukemia. Moreover, KD025 significantly inhibited the efflux of [3H]‑mitoxantrone and hence accumulated higher levels of [3H]‑mitoxantrone in HL60/ABCG2 cells. However, mechanistic research indicated that KD025 did not alter the protein levels and subcellular locations of ABCG2. KD025 may restrain the efflux activity of ABCG2 by obstructing ATPase activity. Taken together, KD025 can sensitize conventional antineoplastic drugs in ABCG2‑overexpressing leukemia cells by blocking the pump function of ABCG2 protein. The present findings may provide a novel and useful combinational therapeutic strategy of KD025 and antineoplastic drugs for leukemia patients with ABCG2‑mediated MDR.
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December-2020
Volume 20 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Jing W, Zhang X, Chen R, Ye X, Zhou M, Li W, Yan W, Xuyun X and Peng J: KD025, an anti‑adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2‑overexpressing leukemia cells. Oncol Lett 20: 309, 2020
APA
Jing, W., Zhang, X., Chen, R., Ye, X., Zhou, M., Li, W. ... Peng, J. (2020). KD025, an anti‑adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2‑overexpressing leukemia cells. Oncology Letters, 20, 309. https://doi.org/10.3892/ol.2020.12172
MLA
Jing, W., Zhang, X., Chen, R., Ye, X., Zhou, M., Li, W., Yan, W., Xuyun, X., Peng, J."KD025, an anti‑adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2‑overexpressing leukemia cells". Oncology Letters 20.6 (2020): 309.
Chicago
Jing, W., Zhang, X., Chen, R., Ye, X., Zhou, M., Li, W., Yan, W., Xuyun, X., Peng, J."KD025, an anti‑adipocyte differentiation drug, enhances the efficacy of conventional chemotherapeutic drugs in ABCG2‑overexpressing leukemia cells". Oncology Letters 20, no. 6 (2020): 309. https://doi.org/10.3892/ol.2020.12172