Korean J Otorhinolaryngol-Head Neck Surg.  2025 Mar;68(3):113-120. 10.3342/kjorl-hns.2023.00962.

Effect of Combined Treatment of Metoclopramide With Platinum-Based Drugs on Apoptosis in AMC-HN4 Cells

• Park JW
• Woo SM
• Jeong JI
• Lee JM
• Lee JW
• Kim DE
• Kwon TK

• KMID: 2565892
• DOI: http://doi.org/10.3342/kjorl-hns.2023.00962

Abstract

Background and Objectives
Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its underlying mechanisms and function in improving the efficiency of chemotherapy are not fully understood. In this study, we investigated the sensitizing effect of metoclopramide on the platinum-based drugs-mediated apoptosis in human head and neck cancer cells.
Subjects and Method
Apoptosis was analyzed using a cell-based cytometer. The protein expression and messenger ribonucleic acid (mRNA) levels were assessed by Western blotting and real-time polymerase chain reaction, respectively.
Results
Metoclopramide sensitized the platinum-based drug (cisplatin and oxaliplatin)-mediated apoptosis in AMC-HN4 cells, but not in normal cells. Mechanistically, we found that metoclopramide decreased Mcl-1 protein expression through post-translational regulation. Moreover, the overexpression of Mcl-1 prevented apoptosis by combined treatment of metoclopramide and platinum-based drugs.
Conclusion
Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

Keyword

Apoptosis; Mcl-1; Metoclopramide; Platinum compound