Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer modelReport as inadecuate




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Journal of Experimental and Clinical Cancer Research

, 33:21

First Online: 20 February 2014Received: 04 December 2013Accepted: 18 February 2014DOI: 10.1186-1756-9966-33-21

Cite this article as: Deng, GH., Liu, J., Zhang, J. et al. J Exp Clin Cancer Res 2014 33: 21. doi:10.1186-1756-9966-33-21

Abstract

BackgroundSunitinib 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.

MethodsThe 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.

ResultsWe 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.

ConclusionsThis 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.

KeywordsTumor Chronic stress Norepinephrine Sunitinib Propranolol Electronic supplementary materialThe online version of this article doi:10.1186-1756-9966-33-21 contains supplementary material, which is available to authorized users.

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Author: Guo-Hua Deng - Jie Liu - Jie Zhang - Ying Wang - Xing-Chen Peng - Yu-Quan Wei - Yu Jiang

Source: https://link.springer.com/







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