Open Access

Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway

  • Authors:
    • Jie Li
    • Wenjing Liu
    • Hongling Hao
    • Qiuyi Wang
    • Liying Xue
  • View Affiliations

  • Published online on: July 9, 2019     https://doi.org/10.3892/ol.2019.10589
  • Pages: 2694-2703
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chronic myelogenous leukemia (CML) is a common hematological malignancy. Some patients progressing to the blast phase develop chemotherapeutic drug resistance. In the authors' previous study, it was found that the mammalian target of rapamycin (mTOR) pathway was activated in CML and that rapamycin inhibited the proliferation of K562 cells. Targeting the mTOR pathway may be used in combination with chemotherapeutic drugs to enhance their efficacy and overcome multidrug resistance. The aim of the present study was to investigate the effects of rapamycin and doxorubicin on K562 cell proliferation following the combination treatment, and further focus on confirming whether rapamycin enhanced the antitumor effects of doxorubicin by downregulating the mTOR/ribosomal protein S6 kinase (p70S6K) pathway. It was found that rapamycin and doxorubicin significantly decreased the viability of K562 cells. The apoptotic cells were more frequently detected in rapamycin and doxorubicin treatment groups (25.50±1.25%). Both drugs decreased Bcl‑2 and increased Bax expression in K562 cells. Rapamycin and doxorubicin also reduced the phosphorylation levels of mTOR and p70S6K. Meanwhile, p70S6K‑targeting small interfering (si)RNA and doxorubicin inhibited cell proliferation and regulated key factors of the cell cycle. In addition, the exposure of cells to p70S6K siRNA and doxorubicin significantly increased cell apoptosis, as compared with single treatment. These results suggested that rapamycin could enhance the antitumor effects of doxorubicin on K562 cells by downregulating mTOR/p70S6K signaling. Targeting the mTOR/p70S6K pathway may be a new therapeutic approach for leukemia.

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September 2019
Volume 18 Issue 3

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

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APA
Li, J., Liu, W., Hao, H., Wang, Q., & Xue, L. (2019). Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway. Oncology Letters, 18, 2694-2703. https://doi.org/10.3892/ol.2019.10589
MLA
Li, J., Liu, W., Hao, H., Wang, Q., Xue, L."Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway". Oncology Letters 18.3 (2019): 2694-2703.
Chicago
Li, J., Liu, W., Hao, H., Wang, Q., Xue, L."Rapamycin enhanced the antitumor effects of doxorubicin in myelogenous leukemia K562 cells by downregulating the mTOR/p70S6K pathway". Oncology Letters 18, no. 3 (2019): 2694-2703. https://doi.org/10.3892/ol.2019.10589