cudc907displayspotentantitumoractivityagainsthumanpancreaticadenocarcinomainvitroandinvivothroughinhibitionofhdac6todownregulatecmycexpression

doi:10.1038/s41401-018-0108-5

	cudc907displayspotentantitumoractivityagainsthumanpancreaticadenocarcinomainvitroandinvivothroughinhibitionofhdac6todownregulatecmycexpression
	Fu Xuhong 1; Zhang Xiong 2; Yang Hong 2; Xu Xiaowei 2; Hu Zonglong 2; Yan Juan 2; Zheng Xingling 2; Wei Rongrui 2; Zhang Zhuqing 2; Tang Shirui 3
刊名	actapharmacologicasinica
	2019
卷号	40 期号:5 页码:677
关键词	CANCER GROWTH TARGET PI3K ACTIVATION
ISSN号	1671-4083
DOI	10.1038/s41401-018-0108-5
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 IC50 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.
资助项目	[Shanghai Talent Development Funds] ; [Open Project of State Key Laboratory of Drug Research] ; [Youth Innovation Promotion Association CAS]
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/288460]
专题	中国科学院上海药物研究所
作者单位	1.南昌大学 2.中国科学院上海药物研究所 3.
推荐引用方式 GB/T 7714	Fu Xuhong,Zhang Xiong,Yang Hong,et al. cudc907displayspotentantitumoractivityagainsthumanpancreaticadenocarcinomainvitroandinvivothroughinhibitionofhdac6todownregulatecmycexpression[J]. actapharmacologicasinica,2019,40(5):677.
APA	Fu Xuhong.,Zhang Xiong.,Yang Hong.,Xu Xiaowei.,Hu Zonglong.,...&Huang Xun.(2019).cudc907displayspotentantitumoractivityagainsthumanpancreaticadenocarcinomainvitroandinvivothroughinhibitionofhdac6todownregulatecmycexpression.actapharmacologicasinica,40(5),677.
MLA	Fu Xuhong,et al."cudc907displayspotentantitumoractivityagainsthumanpancreaticadenocarcinomainvitroandinvivothroughinhibitionofhdac6todownregulatecmycexpression".actapharmacologicasinica 40.5(2019):677.