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Cholesterol esterification inhibition and gemcitabine synergistically suppress pancreatic ductal adenocarcinoma proliferation
Li, Junjie1; Qu, Xiaochao2; Tian, Jie2,3; Zhang, Jian-Ting4; Cheng, Ji-Xin1,5,6
2018-02-28
发表期刊PLOS ONE
卷号13期号:2
文章类型Article
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标题词Science & Technology
DOI10.1371/journal.pone.0193318
关键词[WOS]BREAST-CANCER CELLS ; DRUG-RESISTANCE ; METABOLISM ; OVEREXPRESSION ; GROWTH
收录类别SCI
语种英语
项目资助者DoD Award(W81XWH-14-1-0557) ; National Natural Science Foundation of China(81227901 ; 81530058)
WOS研究方向Science & Technology - Other Topics
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000426276000065
引用统计
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/21984
专题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
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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).
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