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Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells

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收录情况： ◇ SCIE

作者：
Li, Xu[1] * ; Zhu, Feng[1] ; Jiang, Jianxin[2] ; Sun, Chengyi[2] ; Wang, Xin[1] ; Shen, Ming[1] ; Tian, Rui[1] ; Shi, Chengjian[1] ; Xu, Meng[1] ; Peng, Feng[1] ; Guo, Xingjun[1] ; Wang, Min[1] ; Qin, Renyi[1] ;
单位： [1]Huazhong Univ Sci & Technol,Dept Biliary Pancreat Surg,Affiliated Tongji Hosp,Tongji Med Coll,Wuhan 430074,Hubei,Peoples R China [2]Guiyang Med Coll, Affiliated Hosp, Dept Biliary Hepat Surg, Guiyang, Guizhou, Peoples R China
出处：
DOI： 10.1016/j.canlet.2014.11.026
ISSN：

关键词： Withaferin A Oxaliplatin Pancreatic cancer Apoptosis ROS PI3K/AKT pathway

摘要：
Application of oxaliplatin for the treatment of pancreatic cancer (PC) is restricted owing to its toxic side effects and drug resistance. We investigated how withaferin A (WA), a bioactive component isolated from the medicinal plant Withania somnifera, acts synergistically with oxaliplatin on human PC in vitro and in vivo. We found that WA enhanced oxaliplatin-induced growth suppression and apoptosis in PC cells dramatically through a mechanism involving mitochondrial dysfunction and inactivation of the PI3K/AICT pathway. Combination treatment resulted in significant accumulation of intracellular reactive oxygen species (ROS). Pretreatment of cells with the ROS scavenger N-acetylcysteine completely blocked the apoptosis induced by combination treatment, and recovered expression of AKT inactivation, which revealed the important role of ROS in apoptosis and AKT regulation. In vivo, combination therapy showed the strongest anti-tumor effects compared with single agents, without obvious additional toxicity. These results support the notion that combination treatment with oxaliplatin and WA could facilitate development of an effective strategy for PC treatment. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

基金：
National Natural Science Foundation of China [81272659, 81101621, 81160311, 81372353, 81172064, 81301860]; National "Eleventh Five-Year" Scientific and Technological Support Projects [2006BAI02A13-402]; Projects of Science Foundation of Hubei Province [2012FFB02401]; International S&T Cooperation Projects of China [2014DFA31420]; Research Fund of Young Scholars for the Doctoral Program of Higher Education of China [20110142120014]
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外文
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出版当年[2014]版：
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版：
大类 | 1 区 医学
小类 | 2 区 肿瘤学
JCR分区：
出版当年[2013]版：
Q1 ONCOLOGY
最新[2023]版：
Q1 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2013版] 出版当年五年平均 出版前一年[2012版] 出版后一年[2014版]

第一作者：
第一作者单位： [1]Huazhong Univ Sci & Technol,Dept Biliary Pancreat Surg,Affiliated Tongji Hosp,Tongji Med Coll,Wuhan 430074,Hubei,Peoples R China
通讯作者：
推荐引用方式(GB/T 7714)：
Li Xu,Zhu Feng,Jiang Jianxin,et al.Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells[J].CANCER LETTERS.2015,357(1):219-230.doi:10.1016/j.canlet.2014.11.026.
APA：
Li, Xu,Zhu, Feng,Jiang, Jianxin,Sun, Chengyi,Wang, Xin...&Qin, Renyi.(2015).Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells.CANCER LETTERS,357,(1)
MLA：
Li, Xu,et al."Synergistic antitumor activity of withaferin A combined with oxaliplatin triggers reactive oxygen species-mediated inactivation of the PI3K/AKT pathway in human pancreatic cancer cells".CANCER LETTERS 357..1(2015):219-230

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