Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis
文献类型：期刊论文
| 作者 | Miao, Chunxiao1; Lv, Yuanyuan1; Zhang, Wanli1; Chai, Xiaoping1; Feng, Lixing1,2; Fang, Yanfen1,3; Liu, Xuan2; Zhang, Xiongwen1 |
| 刊名 | FRONTIERS IN PHARMACOLOGY
 |
| 出版日期 | 2017-12-12 |
| 卷号 | 8 |
| ISSN号 | 1663-9812 |
| 关键词 | cancer cachexia PDTC C2C12 myotubes 3T3-L1 adipocytes muscle atrophy fat lipolysis |
| DOI | 10.3389/fphar.2017.00915 |
| 文献子类 | Article |
| 英文摘要 | Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-kappa B signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-kappa B signaling, Pyrrolidine dithiocarbamate ( PDTC) was reported to relieve cancer cachexia; however, its mechanism remains largely unknown. In our study, we showed that PDTC attenuated cancer cachexia symptom in C26 tumor bearing mice models in vivo without influencing tumor volume. What's more, PDTC inhibited muscle atrophy and lipolysis in cells models in vitro induced by TNF alpha and C26 tumor medium. PDTC suppressed atrophy of myotubes differentiated from C2C12 by reducing MyoD and upregulating MuRF1, and preserving the expression of perilipin as well as blocking the activation of HSL in 3T3-L1 mature adipocytes. Meaningfully, we observed that PDTC also inhibited p38 MAPK signaling besides the NF-kappa B signaling in cancer cachexia in vitro models. In addition, PDTC also influenced the protein synthesis of skeletal muscle by activating AKT signaling and regulated fat energy metabolism by inhibiting AMPK signaling. Therefore, PDTC primarily influenced different pathways in different tissues. The study not only established a simple and reliable screening drugs model of cancer cachexia in vitro but also provided new theoretical basis for future treatment of cancer cachexia. |
| WOS关键词 | NF-KAPPA-B ; HORMONE-SENSITIVE LIPASE ; MYOSIN HEAVY-CHAIN ; UBIQUITIN LIGASE ATROGIN1/MAFBX ; NECROSIS-FACTOR-ALPHA ; CELL LUNG-CANCER ; SKELETAL-MUSCLE ; TNF-ALPHA ; P38 MAPK ; ACTIVATION |
| 资助项目 | Shanghai Science and Technology Innovation Action Program[15140904800] ; Science and Technology Commission of Shanghai Municipality[14431902700] ; Science and Technology Commission of Shanghai Municipality[16DZ2280100] ; Open Funds of State Key Laboratory of Oncology in South China[HN2016-03] ; National Natural Science Foundation of China[81402953] ; China Postdoctoral Science Foundation[2015T80416] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | FRONTIERS MEDIA SA |
| WOS记录号 | WOS:000417706900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272354]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Fang, Yanfen; Liu, Xuan; Zhang, Xiongwen |
| 作者单位 | 1.East China Normal Univ, Coll Chem & Mol Engn, Shanghai Engn Res Ctr Mol Therapeut & New Drug De, Shanghai, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Biomed Res, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med CAS, Div Antitumor Pharmacol, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Miao, Chunxiao,Lv, Yuanyuan,Zhang, Wanli,et al. Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis[J]. FRONTIERS IN PHARMACOLOGY,2017,8. |
| APA | Miao, Chunxiao.,Lv, Yuanyuan.,Zhang, Wanli.,Chai, Xiaoping.,Feng, Lixing.,...&Zhang, Xiongwen.(2017).Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis.FRONTIERS IN PHARMACOLOGY,8. |
| MLA | Miao, Chunxiao,et al."Pyrrolidine Dithiocarbamate (PDTC) Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis".FRONTIERS IN PHARMACOLOGY 8(2017). |
入库方式： OAI收割
来源：上海药物研究所
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