Effect of Combined Treatment of Metoclopramide With Platinum-Based Drugs on Apoptosis in AMC-HN4 Cells
10.3342/kjorl-hns.2023.00962
- Author:
Jong Won PARK
1
;
Seon Min WOO
;
Jong In JEONG
;
Jae Man LEE
;
Ji Won LEE
;
Dong Eun KIM
;
Taeg Kyu KWON
Author Information
1. Department of Otorhinolaryngology, Keimyung University School of Medicine, Daegu, Korea
- Publication Type:Original Article
- From:Korean Journal of Otolaryngology - Head and Neck Surgery
2025;68(3):113-120
- CountryRepublic of Korea
- Language:Korean
-
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.
