Published in:
Open Access
01-12-2014 | Research
Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model
Authors:
Guo-Hua Deng, Jie Liu, Jie Zhang, Ying Wang, Xing-Chen Peng, Yu-Quan Wei, Yu Jiang
Published in:
Journal of Experimental & Clinical Cancer Research
|
Issue 1/2014
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Abstract
Background
Sunitinib alone exhibits satisfactory efficacy in several mouse homografts and xenografts but unsatisfactory efficacy in many kinds of solid tumors in clinic. Different from animals, receiving a diagnosis of cancer impacts chronic stress on patients. Here, we examine whether norepinephrine (NE), one of the most potent stress related hormones, leads to the difference in the efficacy of sunitinib between clinical and preclinical trials.
Methods
The influence of NE on mouse melanoma B16F1 cells under sunitinib was evaluated in vitro and in vivo. The β-AR/cAMP/PKA (β-adrenoceptor/cyclic adenosine monophosphate/protein kinase A) signaling pathway was also evaluated in human lung adenocarcinoma cells.
Results
We found that NE upregulated the expression of VEGF, IL-8 and IL-6 in vitro and stimulated tumor growth in vivo, which was mediated by β-AR/cAMP/PKA signaling pathway and could be inhibited by propranolol, a β-blocker for hypertension for decades.
Conclusions
This research indicates exogenous norepinephrine attenuates the efficacy of sunitinib, and a combination of sunitinib and propranolol might be suggested as a new strategy in solid tumor in clinic.