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Article

Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5

  • Authors:
    • Fusen Peng
    • Hailin Zhang
    • Youhong Du
    • Pingqing Tan
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Head and Neck Surgery, Hunan Tumor Hospital, Changsha, Hunan 410013, P.R. China, Department of Otolaryngology Head and Neck Surgery, Loudi Central Hospital, Loudi, Hunan 417000, P.R. China
  • Pages: 4767-4776
    |
    Published online on: January 5, 2018
       https://doi.org/10.3892/mmr.2018.8376
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Abstract

Cisplatin and cetuximab, an anti‑epidermal growth factor receptor (EGFR) monoclonal humanized antibody, have been used for treatment of laryngeal squamous cell carcinoma (LSCC). It has been demonstrated that cisplatin and inhibition of EGFR signaling may induce endoplasmic reticulum (ER) stress‑associated apoptosis. However, ER protein thioredoxin domain‑containing protein 5 (TXNDC5) reportedly protects cells from ER stress‑associated apoptosis. The present study investigated the interaction between cisplatin, cetuximab and TXNDC5 on ER stress‑associated apoptosis in LSCC cells. AMC‑HN‑8 human LSCC cells with or without TXNDC5 overexpression or knockdown were treated with cisplatin (5, 10, 20 and 40 µM) and/or cetuximab (10, 50, 100 and 150 µg/ml), for 12, 24, 36 and 48 h. Cisplatin and cetuximab concentration‑ and time‑dependently increased and decreased the expression of TXNDC5 in AMC‑HN‑8 cells, respectively. Knockdown of TXNDC5 markedly augmented cisplatin‑induced levels of CCAAT/enhancer‑binding protein homologous protein (CHOP), caspase‑3 activity and apoptosis; while overexpression of TXNDC5 largely eliminated cetuximab‑induced levels of CHOP, caspase‑3 activity and apoptosis. Cisplatin and cetuximab demonstrated a combinatorial effect on increasing the levels of CHOP, caspase‑3 activity and apoptosis, which was largely eliminated by overexpression of TXNDC5 or a reactive oxygen species (ROS) scavenger/antagonist. In addition, promoter/luciferase reporter assays revealed that cisplatin and cetuximab regulated the expression of TXNDC5 at the gene transcription/promoter level. In conclusion, the findings suggested that ER stress‑associated apoptosis is a major mechanism underlying the apoptotic effect of cisplatin and cetuximab on LSCC cells; cetuximab enhanced cisplatin‑induced ER stress‑associated apoptosis in LSCC cells largely by inhibiting the expression of TXNDC5 and thereby increasing ROS production; cisplatin and cetuximab had stimulatory and inhibitory effects on the TXNDC5 gene promoter, respectively. The present study offered novel insights into the pharmacological effects of cisplatin and cetuximab on LSCC. It also suggested that TXNDC5 may be a potential therapeutic target for LSCC.
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Copy and paste a formatted citation
Spandidos Publications style
Peng F, Zhang H, Du Y and Tan P: Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5. Mol Med Rep 17: 4767-4776, 2018.
APA
Peng, F., Zhang, H., Du, Y., & Tan, P. (2018). Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5. Molecular Medicine Reports, 17, 4767-4776. https://doi.org/10.3892/mmr.2018.8376
MLA
Peng, F., Zhang, H., Du, Y., Tan, P."Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5". Molecular Medicine Reports 17.3 (2018): 4767-4776.
Chicago
Peng, F., Zhang, H., Du, Y., Tan, P."Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5". Molecular Medicine Reports 17, no. 3 (2018): 4767-4776. https://doi.org/10.3892/mmr.2018.8376
Copy and paste a formatted citation
x
Spandidos Publications style
Peng F, Zhang H, Du Y and Tan P: Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5. Mol Med Rep 17: 4767-4776, 2018.
APA
Peng, F., Zhang, H., Du, Y., & Tan, P. (2018). Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5. Molecular Medicine Reports, 17, 4767-4776. https://doi.org/10.3892/mmr.2018.8376
MLA
Peng, F., Zhang, H., Du, Y., Tan, P."Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5". Molecular Medicine Reports 17.3 (2018): 4767-4776.
Chicago
Peng, F., Zhang, H., Du, Y., Tan, P."Cetuximab enhances cisplatin-induced endoplasmic reticulum stress-associated apoptosis in laryngeal squamous cell carcinoma cells by inhibiting expression of TXNDC5". Molecular Medicine Reports 17, no. 3 (2018): 4767-4776. https://doi.org/10.3892/mmr.2018.8376
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