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Article Open Access

Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction

  • Authors:
    • Kuiyuan Liu
    • Jia Liu
    • Tiebao Meng
    • Nan Wu
    • Juntao Liu
    • Mingxu Qiao
    • Liangyi Dong
    • Jingeng Liu
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Intensive Care Unit, Sun Yat sen University Cancer Center, Guangzhou, Guangdong 510030, P.R. China, Department of Medical Imaging, Sun Yat sen University Cancer Center, Guangzhou, Guangdong 510030, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 74
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    Published online on: January 24, 2025
       https://doi.org/10.3892/mmr.2025.13439
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Abstract

The present study investigated the sensitization mechanism of triptolide (TPL) in esophageal squamous cell carcinoma (ESCC) resistant to cis‑diamminedichloroplatinum (CDDP). CDDP‑resistant TE‑1/CDDP and KYSE30/CDDP cells were created using an incremental drug concentration approach. TPL and CDDP treatment conditions were screened based on the Cell Counting Kit‑8 cell viability assay and cell proliferation was detected using 5‑ethynyl‑2'‑deoxyuridine and clone formation assays. Flow cytometry combined with Hoechst 33258 staining was used to assess cell cycle progression and apoptosis. Scratch healing assay, Transwell assay and western blotting were used to investigate the malignant behaviors of the cells. Changes in cellular glycolysis were investigated by measuring glucose uptake, lactate production and the levels of related regulatory factors. Changes in mitochondrial function were examined by detecting ATP and reactive oxygen species levels, as well as mitochondrial membrane potential and cytochrome c release. Furthermore, a nude mouse subcutaneous graft tumor model assay was used to assess the in vivo effect of TPL. In vitro dosages of TPL and CDDP were tested at 2 nM and 4 µM, respectively. Notably, TPL decreased the proliferation, migration, invasion and epithelial‑mesenchymal transition of CDDP‑resistant ESCC cells, increased their apoptosis and significantly suppressed tumor growth in a nude mouse model of ESCC. TPL was shown to have a strong CDDP‑sensitizing effect in vitro and in vivo and its mechanism may involve inhibiting anaerobic glycolysis and causing mitochondrial energy metabolism impairment to induce apoptosis. In conclusion, TPL may be considered a potential CDDP sensitizer with substantial clinical implications for ESCC therapy.
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Copy and paste a formatted citation
Spandidos Publications style
Liu K, Liu J, Meng T, Wu N, Liu J, Qiao M, Dong L and Liu J: Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction. Mol Med Rep 31: 74, 2025.
APA
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M. ... Liu, J. (2025). Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction. Molecular Medicine Reports, 31, 74. https://doi.org/10.3892/mmr.2025.13439
MLA
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M., Dong, L., Liu, J."Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction". Molecular Medicine Reports 31.3 (2025): 74.
Chicago
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M., Dong, L., Liu, J."Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction". Molecular Medicine Reports 31, no. 3 (2025): 74. https://doi.org/10.3892/mmr.2025.13439
Copy and paste a formatted citation
x
Spandidos Publications style
Liu K, Liu J, Meng T, Wu N, Liu J, Qiao M, Dong L and Liu J: Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction. Mol Med Rep 31: 74, 2025.
APA
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M. ... Liu, J. (2025). Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction. Molecular Medicine Reports, 31, 74. https://doi.org/10.3892/mmr.2025.13439
MLA
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M., Dong, L., Liu, J."Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction". Molecular Medicine Reports 31.3 (2025): 74.
Chicago
Liu, K., Liu, J., Meng, T., Wu, N., Liu, J., Qiao, M., Dong, L., Liu, J."Triptolide reverses cis‑diamminedichloroplatinum resistance in esophageal squamous cell carcinoma by suppressing glycolysis and causing mitochondrial malfunction". Molecular Medicine Reports 31, no. 3 (2025): 74. https://doi.org/10.3892/mmr.2025.13439
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