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Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN

  • Authors:
    • Guanhua Zhang
    • Ye-Hua Gan
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, Peking University School and Hospital of Stomatology, Haidian, Beijing 100081, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2657-2666
    |
    Published online on: September 21, 2017
       https://doi.org/10.3892/or.2017.5981
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Abstract

Chemotherapy is one of the most effective non-surgical treatments for various types of tumor. Identifying different combinations of antitumor agents that can produce synergistic antitumor effects remains an important clinical strategy. In the present study, we showed that the combination of histone deacetylase 6 (HDAC6) inhibitor tubastatin A together with cyclooxygenase-2 (COX-2) inhibitor celecoxib resulted in synergistic antitumor effects in CAL 27 and SACC-83 cells. Treatment with celecoxib alone promoted the membrane translocation of phosphatase and tensin homolog (PTEN), indicating PTEN activation, and consequently led to protein kinase B (AKT) dephosphorylation (inactivation). Similarly, treatment with an HDAC6 inhibitor alone promoted PTEN membrane translocation and correspondingly dephosphorylated AKT. The combination of celecoxib and an HDAC6 inhibitor synergistically increased PTEN membrane translocation and inactivated AKT. Moreover, celecoxib enhanced the HDAC6 inhibitor-induced antitumor effects in PTEN-deficient U-87 MG cells that had been stably transfected with wild-type PTEN, but not in the same cell line stably transfected with mutant PTEN-K163R, which cannot be activated by HDAC6 inhibitors. In summary, the results indicated that the COX-2 inhibitor celecoxib enhanced the HDAC6 inhibitor-induced antitumor effects by activating the PTEN/AKT signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang G and Gan Y: Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN. Oncol Rep 38: 2657-2666, 2017.
APA
Zhang, G., & Gan, Y. (2017). Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN. Oncology Reports, 38, 2657-2666. https://doi.org/10.3892/or.2017.5981
MLA
Zhang, G., Gan, Y."Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN". Oncology Reports 38.5 (2017): 2657-2666.
Chicago
Zhang, G., Gan, Y."Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN". Oncology Reports 38, no. 5 (2017): 2657-2666. https://doi.org/10.3892/or.2017.5981
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang G and Gan Y: Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN. Oncol Rep 38: 2657-2666, 2017.
APA
Zhang, G., & Gan, Y. (2017). Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN. Oncology Reports, 38, 2657-2666. https://doi.org/10.3892/or.2017.5981
MLA
Zhang, G., Gan, Y."Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN". Oncology Reports 38.5 (2017): 2657-2666.
Chicago
Zhang, G., Gan, Y."Synergistic antitumor effects of the combined treatment with an HDAC6 inhibitor and a COX-2 inhibitor through activation of PTEN". Oncology Reports 38, no. 5 (2017): 2657-2666. https://doi.org/10.3892/or.2017.5981
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