Down-Regulation of Human Epidermal Growth Factor Receptor 2/neu Oncogene by Corosolic Acid Induces Cell Cycle Arrest and Apoptosis in NCI-N87 Human Gastric Cancer Cells
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概要
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Overexpression/amplification of human epidermal growth factor receptor (HER)2/neu (erbB-2) oncogene plays a causal role in carcinogenesis and correlates with a poor clinical prognosis. However, little is known about HER2 in gastric cancer. In this study, we explored the pharmacological activities of natural triterpenoid corosolic acid (CRA) in HER2 signaling and its role in gastric cancer development and progression. In this study, CRA dramatically inhibited HER2 expression in a dose- and time-dependent manner, effectively inhibited cell proliferation, and induced G0/G1 arrest through the induction of p27kip1 and cyclin D1 down-regulation. CRA exposure enhanced apoptotic cell death, as confirmed by caspase-3 and poly (ADP-ribose) polymerase cleavage activities. CRA inhibited signaling pathways downstream of HER2, including phospho-proteins such as Akt and Erk. In addition, CRA combined with adriamycin and 5-fluorouracil enhanced this growth inhibition, but not with docetaxel and paclitaxel. These findings demonstrate that CRA suppresses HER2 expression, which in turn promotes cell cycle arrest and apoptotic cell death of gastric cancer cells, providing a rationale for future clinical trials of CRA in the treatment of HER2-positive gastric cancers.
著者
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KIM Ji
Department of Polymer Science and Engineering, Kumoh National Institute of Technology
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Thuong Phuong
Vietnam National Inst. Of Medicinal Materials
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Kim Ji
Department Of Anesthesiology And Pain Medicine Gachon Medical School Gil Medical Center
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Sul Ji
Department of Surgery, Chungnam National University Hospital
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Lee Myung
Regional Cancer Inst. Chungnam National Univ. Hospital
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Cha Eun
Regional Cancer Institute, Chungnam National University Hospital
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Ahn Moon
Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University Sc
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Sul Ji
Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University School of Medicine
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Kim Ji
Department of Advanced Materials Engineering, Sangju National University, Kyeongbuk 742-711, Korea
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Ahn Moon
Department of Surgery and Research Institute for Medicinal Sciences, Chungnam National University School of Medicine
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Thuong Phuong
Vietnam National Institute of Medicinal Materials
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Lee Myung
Regional Cancer Institute, Chungnam National University Hospital
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