Dihydroartemisinin inactivates NF-κB and potentiates the anti-tumor effect of gemcitabine on pancreatic cancer both in vitro and in vivo

被引:165
作者
Wang, Shuang-Jia [1 ]
Gao, Yue [2 ]
Chen, Hua [1 ]
Kong, Rui [1 ]
Jiang, Hong-Chi [1 ]
Pan, Shang-Ha [1 ]
Xue, Dong-Bo [1 ]
Bai, Xue-Wei [1 ]
Sun, Bei [1 ]
机构
[1] Harbin Med Coll, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Harbin, Peoples R China
[2] Sahlgrens Univ Hosp, Dept Clin Chem, S-41345 Gothenburg, Sweden
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; Dihydroartemisinin; Gemcitabine; Nuclear factor-kappa B; PHASE-III TRIAL; SESQUITERPENE LACTONES; ARTEMISININ DERIVATIVES; TRANSCRIPTION FACTOR; MEDIATED APOPTOSIS; MOLECULAR EVIDENCE; SIGNALING PATHWAY; ORTHOTOPIC MODEL; LUNG-CANCER; CELL-GROWTH;
D O I
10.1016/j.canlet.2010.01.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gemcitabine is currently the best known chemotherapeutic option available for pancreatic cancer, but the tumor returns de novo with acquired resistance over time, which becomes a major issue for all gemcitabine-related chemotherapies. In this study, for the first time, we demonstrated that dihydroartemisinin (DHA) enhances gemcitabine-induced growth inhibition and apoptosis in both BxPC-3 and PANC-1 cell lines in vitro. The mechanism is at least partially due to DHA deactivates gemcitabine-induced NF-kappa B activation, so as to decrease tremendously the expression of its target gene products, such as c-myc, cyclin D1, Bcl-2, Bcl-xL. In our in vivo studies, gemcibabine also manifested remarkably enhanced anti-tumor effect when combined with DHA, as manifested by significantly increased apoptosis, as well as decreased Ki-67 index, NF-kappa B activity and its related gene products, and predictably, significantly reduced tumor volume. We concluded that inhibition of gemcitabine-induced NF-kappa B activation is one of the mechanisms that DHA dramatically promotes its anti-tumor effect on pancreatic cancer. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:99 / 108
页数:10
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