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.
Published Version
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