두경부 암세포에서 Metoclopramide와 Platinum 기반 항암제의 병용 처리에 의한 세포 사멸 증진 효과 (Effect of Combined Treatment of Metoclopramide With Platinum-Based Drugs on Apoptosis in AMC-HN4 Cells)

서지정보

· 발행기관 : 대한이비인후과학회
· 수록지 정보 : 대한이비인후-두경부외과학회지 / 68권 / 3호 / 113 ~ 120페이지
· 저자명 : 박종원, 김동은, 우선민, 정종인, 이재만, 이지원, 권택규

초록

Background and Objectives Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its under- lying mechanisms and function in improving the efficiency of chemotherapy are not fully un- derstood. In this study, we investigated the sensitizing effect of metoclopramide on the plati- num-based drugs-mediated apoptosis in human head and neck cancer cells.
Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein ex- pression 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)-me- diated 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 meto- clopramide and platinum-based drugs.
Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

영어초록

Background and Objectives Metoclopramide is an antagonist of dopamine D2 receptor and is capable of alleviating chemotherapy-induced nausea and vomiting. However, its under- lying mechanisms and function in improving the efficiency of chemotherapy are not fully un- derstood. In this study, we investigated the sensitizing effect of metoclopramide on the plati- num-based drugs-mediated apoptosis in human head and neck cancer cells.
Subjects and Method Apoptosis was analyzed using a cell-based cytometer. The protein ex- pression 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)-me- diated 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 meto- clopramide and platinum-based drugs.
Conclusion Metoclopramide induced proteasome-mediated Mcl-1 downregulation, resulting in increased sensitivity to platinum-based drugs.

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