CASIA OpenIR  > 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, Junjie1; Qu, Xiaochao2; Tian, Jie2,3; Zhang, Jian-Ting4; Cheng, Ji-Xin1,5,6
Source PublicationPLOS ONE
2018-02-28
Volume13Issue:2
SubtypeArticle
AbstractRecent 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 HeadingsScience & Technology
DOI10.1371/journal.pone.0193318
WOS KeywordBREAST-CANCER CELLS ; DRUG-RESISTANCE ; METABOLISM ; OVEREXPRESSION ; GROWTH
Indexed BySCI
Language英语
Funding OrganizationDoD Award(W81XWH-14-1-0557) ; National Natural Science Foundation of China(81227901 ; 81530058)
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000426276000065
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/21984
Collection中国科学院分子影像重点实验室
Affiliation1.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
Recommended Citation
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).
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