CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression
文献类型：期刊论文
| 作者 | Fu, Xu-Hong2; Zhang, Xiong1; Yang, Hong1; Xu, Xiao-Wei1; Hu, Zong-Long1; Yan, Juan1; Zheng, Xing-Ling1; Wei, Rong-Rui1; Zhang, Zhu-Qing1; Tang, Shi-Rui |
| 刊名 | Acta pharmacologica Sinica
 |
| 出版日期 | 2018-09-17 |
| ISSN号 | 1745-7254 |
| DOI | 10.1038/s41401-018-0108-5 |
| 文献子类 | Article |
| 英文摘要 | Pancreatic adenocarcinoma is a highly malignant cancer that often involves a deregulation of c-Myc. It has been shown that c-Myc plays a pivotal role in the regulation of a variety of physiological processes and is involved in early neoplastic development, resulting in poor progression. Hence, suppression of c-Myc overexpression is a potential strategy for pancreatic cancer therapy. CUDC-907 is a novel dual-acting inhibitor of phosphoinositide 3-kinase (PI3K) and histone deacetylase (HDAC). It has shown potential efficiency in patients with lymphoma, multiple myeloma, or thyroid cancer, as well as in solid tumors with c-Myc alterations, but the evidence is lacking for how CUDC-907 regulates c-Myc. In this study, we investigated the effect of CUDC-907 on human pancreatic cancer cells in vitro and in vivo. Our results showed that CUDC-907 potently inhibited the proliferation of 9 pancreatic cancer cell lines in vitro with IC values ranging from 6.7 to 54.5 nM. Furthermore, we revealed the antitumor mechanism of CUDC-907 in Aspc-1, PANC-1, and Capan-1 pancreatic cancer cells: it suppressed the HDAC6 subunit, thus downregulating c-Myc protein levels, which was a mode of action distinct from the existing mechanisms. Consistently, the extraordinary antitumor activity of CUDC-907 accompanied by downregulation of c-Myc and Ki67 expression in tumor tissue was observed in a human pancreatic cancer Aspc-1 xenograft nude mouse model in vivo. Our results suggest that CUDC-907 can be a valuable therapeutic option for treating pancreatic adenocarcinoma. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266562]  |
| 专题 | 新药研究国家重点实验室 药理学第一研究室 |
| 通讯作者 | Geng, Mei-Yu; Huang, Xun |
| 作者单位 | 1.Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China 2.College of Pharmacy, Nanchang University, Nanchang, 330006, China; |
| 推荐引用方式 GB/T 7714 | Fu, Xu-Hong,Zhang, Xiong,Yang, Hong,et al. CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression[J]. Acta pharmacologica Sinica,2018. |
| APA | Fu, Xu-Hong.,Zhang, Xiong.,Yang, Hong.,Xu, Xiao-Wei.,Hu, Zong-Long.,...&Huang, Xun.(2018).CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression.Acta pharmacologica Sinica. |
| MLA | Fu, Xu-Hong,et al."CUDC-907 displays potent antitumor activity against human pancreatic adenocarcinoma in vitro and in vivo through inhibition of HDAC6 to downregulate c-Myc expression".Acta pharmacologica Sinica (2018). |
入库方式： OAI收割
来源：上海药物研究所
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