机构：[a]Department of Breast Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.[b]Department of Neurology, the First Affiliated Hospital of Soochow University, Suzhou, China.[c]Department of Radiotherapy and Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China.[d]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021, China.[e]Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, China.
Here we reported that co-administration of docetaxel and a cell-permeable short-chain ceramide (C6) resulted in a striking increase in growth inhibition and apoptosis in primary and transformed breast cells (MCF-7 and MDA-231), which were associated with mitochondrial permeability transition pore (mPTP) opening, a significant reactive oxygen species (ROS) production and the pro-apoptotic AMP-Protein Kinase (AMPK) as well as c-Jun N-terminal kinases (JNK) activations. Contrarily, the mPTP blocker sanglifehrin A (SfA) or the ROS scavenger N-acetyl-L-cysteine (NAC) largely inhibited co-administration-induced cytotoxicity. Further, cyclosporin A (CsA), the inhibitor of cyclophilin-D (Cyp-D, the key mPTP component), as well as Cyp-D RNA silencing also suppressed breast cancer cell death by the co-treatment, while cells overexpressing Cyp-D showed hypersensitivity to docetaxel. Meanwhile, JNK and AMPK inhibition alleviated cell death induced by the co-administration in cultured breast cancer cells. Significantly, C6 ceramide plus docetaxel caused dramatic human epidermal growth factor receptor (HER)-1/-2 degradation and downstream Akt/Erk inhibition in HER-2 expressing MDA-231 cells. These in vitro findings provide confidence in support of further development of C6 ceramide as an adjunct of docetaxel for the treatment of the metastatic breast cancer. (C) 2015 Elsevier Inc. All rights reserved.
基金：
This work was supported by the National Natural Science Founda- tion (Nos. 31371139 and 81302195), Natural Science Foundation of Jiangsu Province (No. BK20130301), by Jiangsu Provincial Special Program of Clinical Medical Science (BL2014040).
第一作者机构：[a]Department of Breast Surgery, the Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China.
共同第一作者：
通讯作者：
通讯机构：[d]Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021, China.[*1]Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Soochow University,185 Ju-qianStreet,Tian-ning District, Changzhou City,Jiangsu,China,213003.
推荐引用方式(GB/T 7714)：
Lan Yang,Li-yun Zheng,Ye Tian,et al.C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study[J].EXPERIMENTAL CELL RESEARCH.2015,332(1):47-59.doi:10.1016/j.yexcr.2014.12.017.
APA：
Lan Yang,Li-yun Zheng,Ye Tian,Zhi-qing Zhang,Wan-li Dong...&Cong Cao.(2015).C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study.EXPERIMENTAL CELL RESEARCH,332,(1)
MLA：
Lan Yang,et al."C6 ceramide dramatically enhances docetaxel-induced growth inhibition and apoptosis in cultured breast cancer cells: A mechanism study".EXPERIMENTAL CELL RESEARCH 332..1(2015):47-59
