期刊
CANCER LETTERS
卷 291, 期 1, 页码 90-98出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2009.10.001
关键词
Pancreatic cancer; Nuclear factor-kappa B; Gemcitabine; Small interference RNA
类别
资金
- Chinese Ministry of Education [NCET-07-0248]
- Scientific Foundation for Prominent Youth of Heilongjiang Province, China [JC200717]
- National Natural Scientific Foundation of China [30571808, 30872987]
The clinical benefit of gemcitabine for pancreatic cancer is low due to chemoresistance. Nuclear factor (NF)-kappa B, constitutively activated in pancreatic cancer, is a therapeutic target as it upregulates expression of genes controlling proliferation, apoptosis and angiogenesis. This study aimed to investigate whether downregulation of the p65 subunit of NE-kappa B by siRNA could enhance the efficacy of gemcitabine to treat pancreatic cancer. p65 siRNA synergized with gemcitabine to inhibit the proliferation and induce the apoptosis of pancreatic cancer cells in vitro and in vivo, and suppress the growth and angiogenesis of pancreatic tumors in nude mice. The mechanisms involved inhibition of NE-kappa B activity and consequent inhibition of Bcl-2, cyclin D1 and VEGF, and activation of caspase-3. The results suggest that downregulation of NF-kappa B p65 potentiates the efficacy of gemcitabine in combating pancreatic cancer. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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