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

21Citations
Citations of this article
22Readers
Mendeley users who have this article in their library.

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 concentrationand 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.

References Powered by Scopus

Analysis of relative gene expression data using real-time quantitative PCR and the 2<sup>-ΔΔC</sup>T method

149839Citations
N/AReaders
Get full text

Cancer statistics, 2009

10121Citations
N/AReaders
Get full text

The unfolded protein response: From stress pathway to homeostatic regulation

4674Citations
N/AReaders
Get full text

Cited by Powered by Scopus

Curcumin enhances cisplatin-induced human laryngeal squamous cancer cell death through activation of TRPM2 channel and mitochondrial oxidative stress

58Citations
N/AReaders
Get full text

PDIA4: The basic characteristics, functions and its potential connection with cancer

54Citations
N/AReaders
Get full text

Metabolic, anti-apoptotic and immune evasion strategies of primary human myeloma cells indicate adaptations to hypoxia

38Citations
N/AReaders
Get full text

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Cite

CITATION STYLE

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(3), 4767–4776. https://doi.org/10.3892/mmr.2018.8376

Readers over time

‘18‘19‘21‘22‘23‘24036912

Readers' Seniority

Tooltip

PhD / Post grad / Masters / Doc 7

78%

Researcher 2

22%

Readers' Discipline

Tooltip

Medicine and Dentistry 6

46%

Biochemistry, Genetics and Molecular Bi... 4

31%

Agricultural and Biological Sciences 2

15%

Neuroscience 1

8%

Article Metrics

Tooltip
Social Media
Shares, Likes & Comments: 6

Save time finding and organizing research with Mendeley

Sign up for free
0