Journal
CANCER LETTERS
Volume 293, Issue 1, Pages 99-108Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2010.01.001
Keywords
Pancreatic cancer; Dihydroartemisinin; Gemcitabine; Nuclear factor-kappa B
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Funding
- Chinese Ministry of Education [NCET-07-0248]
- Science Foundation for Excellent Youth of Heilongjiang Province, China [JC200717]
- National Natural Science Foundation of China [30901437, 30972907]
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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.
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