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Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide

  • Authors:
    • Nan Wang
    • Peining Zhu
    • Renxuan Huang
    • Liankun Sun
    • Delu Dong
    • Yufei Gao
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130000, P.R. China, Key Laboratory of Pathobiology, Ministry of Education, Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1246
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    Published online on: September 2, 2021
       https://doi.org/10.3892/etm.2021.10681
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Abstract

Glioma is a common malignant tumor of the central nervous system, accounting for ~50% of intracranial tumors. The current standard therapy for glioma is surgical resection followed by postoperative adjuvant radiotherapy and temozolomide (TMZ) chemotherapy. However, resistance to TMZ is one of the factors affecting prognosis. It has been reported that TNF receptor‑associated protein 1 (TRAP1) is overexpressed in numerous types of tumor and that interfering with its function may abrogate chemotherapy resistance. TRAP1 inhibitor Gamitrinib triphenylphosphonium (G‑TPP) and shRNA were used in the present study to suppress the function of this molecule in glioblastoma multiforme (GBM) cell lines. MTT assay was performed to evaluate the combined effect of G‑TPP and TMZ treatment. To investigate the underlying mechanism responsible for this combined effect, the mitochondrial unfolded protein response (mtUPR), mitophagy, mitochondrial fusion and reactive oxygen species (ROS) were quantified using western blotting and immunofluorescence techniques. TMZ treatment induced apoptosis in GBM cells by activating the p53 pathway, whilst simultaneously downregulating mitophagy and enhancing mitochondrial fusion. The latter may occur in order to compensate for the defect caused by downregulated mitophagy. Suppressing the function of TRAP1 disturbed this compensatory mechanism by inducing mtUPR, which resulted in a burst of ROS formation and sensitized the GBM cells to the effects of TMZ treatment. Thus, suppressing the function of TRAP1 sensitized GBM cells to TMZ lysis by inducing mtUPR and the subsequent ROS burst. TRAP1 is therefore considered to be a promising target for GBM therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Wang N, Zhu P, Huang R, Sun L, Dong D and Gao Y: Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Exp Ther Med 22: 1246, 2021.
APA
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., & Gao, Y. (2021). Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Experimental and Therapeutic Medicine, 22, 1246. https://doi.org/10.3892/etm.2021.10681
MLA
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., Gao, Y."Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide". Experimental and Therapeutic Medicine 22.5 (2021): 1246.
Chicago
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., Gao, Y."Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1246. https://doi.org/10.3892/etm.2021.10681
Copy and paste a formatted citation
x
Spandidos Publications style
Wang N, Zhu P, Huang R, Sun L, Dong D and Gao Y: Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Exp Ther Med 22: 1246, 2021.
APA
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., & Gao, Y. (2021). Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Experimental and Therapeutic Medicine, 22, 1246. https://doi.org/10.3892/etm.2021.10681
MLA
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., Gao, Y."Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide". Experimental and Therapeutic Medicine 22.5 (2021): 1246.
Chicago
Wang, N., Zhu, P., Huang, R., Sun, L., Dong, D., Gao, Y."Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide". Experimental and Therapeutic Medicine 22, no. 5 (2021): 1246. https://doi.org/10.3892/etm.2021.10681
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