Title: Cholesterol Esterification Inhibition and Gemcitabine Synergistically Suppress Pancreatic Ductal Adenocarcinoma Proliferation
Authors: Li, JJ; Qu, XC; Tian, J; Zhang, JT; Cheng, JX
Author Full Names: Li, Junjie; Qu, Xiaochao; Tian, Jie; Zhang, Jian-Ting; Cheng, Ji-Xin
Source: PLOS ONE, 13 (2):10.1371/journal.pone.0193318 FEB 28 2018
Language: English
Abstract: 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.
ISSN: 1932-6203
Article Number: e0193318
IDS Number: FX7ND
Unique ID: WOS:000426276000065
PubMed ID: 29489864