Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation

doi:10.1371/journal.pone.0193318

CORC > 自动化研究所 > 中国科学院自动化研究所 > 中国科学院分子影像重点实验室

	Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation
	Li, Junjie 1; Qu, Xiaochao 2; Tian, Jie2,3 ; Zhang, Jian-Ting 4; Cheng, Ji-Xin 1,5,6
刊名	PLOS ONE
	2018-02-28
卷号	13 期号:2
DOI	10.1371/journal.pone.0193318
文献子类	Article
英文摘要	Recent advances have recognized metabolic reprogramming as an underlying mechanism for cancer drug resistance. However, the role of cholesterol metabolism in drug resistance remain elusive. Herein, we report an increased accumulation of cholesteryl ester in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cells. A potent inhibitor of acylCoA cholesterol acyltransferase-1 (ACAT-1), avasimibe, effectively suppressed proliferation of gemcitabine-resistant PDAC cells. Combination of avasimibe and gemcitabine showed strong synergistic effect in suppressing PDAC cell viability in vitro and tumor growth in vivo. Immunoblotting analysis suggests downregulation of Akt by avasimibe is likely to contribute to the synergism. Collectively, our study demonstrates a new combinational therapeutic strategy to overcome gemcitabine resistance for PDAC treatment.
WOS关键词	BREAST-CANCER CELLS ; DRUG-RESISTANCE ; METABOLISM ; OVEREXPRESSION ; GROWTH
WOS研究方向	Science & Technology - Other Topics
语种	英语
WOS记录号	WOS:000426276000065
资助机构	DoD Award(W81XWH-14-1-0557) ; National Natural Science Foundation of China(81227901 ; 81530058)
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/21984]
专题	自动化研究所_中国科学院分子影像重点实验室
作者单位	1.Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA 2.Xidian Univ, Sch Life Sci & Technol, Xian, Shaanxi, Peoples R China 3.Chinese Acad Sci, Inst Automat, Beijing, Peoples R China 4.Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA 5.Purdue Univ, Ctr Canc Res, W Lafayette, IN 47907 USA 6.Boston Univ, Dept Biomed Engn, Dept Elect & Comp Engn, Boston, MA 02215 USA
推荐引用方式 GB/T 7714	Li, Junjie,Qu, Xiaochao,Tian, Jie,et al. Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation[J]. PLOS ONE,2018,13(2).
APA	Li, Junjie,Qu, Xiaochao,Tian, Jie,Zhang, Jian-Ting,&Cheng, Ji-Xin.(2018).Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation.PLOS ONE,13(2).
MLA	Li, Junjie,et al."Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation".PLOS ONE 13.2(2018).