Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition
机构：[1]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China江苏省人民医院[2]Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China江苏省人民医院[3]Department of Otolaryngology, The First Affiliated Hospitalof Nanjing Medical University, Nanjing, Jiangsu, China[4]Clinical Experiment Center, The First Affiliated Hospital of NanjingMedical University, Nanjing, Jiangsu, China外科系统耳鼻咽喉科江苏省人民医院[5]Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu,China江苏省人民医院[6]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Instituteof Dermatology, Kunming, Yunnan, China内科科室皮肤科昆明医科大学附属第一医院[7]Department of Dermatology, The Affiliated BenQ Hospital of Nanjing MedicalUniversity, Nanjing, Jiangsu, China内科科室皮肤科昆明医科大学附属第一医院
New chemotherapy-enhancing strategies are needed for better cancer therapy. Previous studies suggest that exogenous cell-permeable C6 ceramide may be a useful adjunct to the anti-tumor effects of chemotherapeutic agents (such as Taxol) against multiple cancers. Here we demonstrate that exogenous cell-permeable C6 ceramide largely sensitizes multiple progressive cancer cell lines to Doxorubicin-induced cell death and apoptosis. We found for the first time that Doxorubicin induces AMP-activated protein kinase (AMPK) activation in a reactive oxygen species-dependent manner. Activation of AMPK contributes to Doxorubicin-induced cancer cell death and apoptosis. Inhibition of AMPK by small interfering RNA knockdown or a pharmacological inhibitor reduces Doxorubicin-induced cancer cell apoptosis, whereas AMPK activator AICAR enhances it. Importantly, we found that C6 ceramide largely enhances Doxorubicin-induced activation of AMPK, which leads to mTOR complex 1 inhibition and chemo-sensitization. Our data suggest that the combination of C6 ceramide with traditional chemotherapy drugs such as Doxorubicin may have the potential to be used as a new therapeutic intervention against multiple cancers. Oncogene (2010) 29, 6557-6568; doi:10.1038/onc.2010.379; published online 30 August 2010
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30271195, 30671894]
第一作者机构：[1]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China[*3]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China.
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Dermatology, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210019, Jiangsu, China.[*2]Department of Dermatology, The First Affiliated Hospital of Kunming Medical University, Yunnan Provincial Institute of Dermatology, Kunming, Yunnan, China.[*3]Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210024, Jiangsu, China.
推荐引用方式(GB/T 7714)：
Ji C.,Yang B.,Yang Y-L,et al.Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition[J].ONCOGENE.2010,29(50):6557-6568.doi:10.1038/onc.2010.379.
APA：
Ji, C.,Yang, B.,Yang, Y-L,He, S-H,Miao, D-S...&Bi, Z-G.(2010).Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition.ONCOGENE,29,(50)
MLA：
Ji, C.,et al."Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition".ONCOGENE 29..50(2010):6557-6568
医学