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01.12.2014 | Research | Ausgabe 1/2014 Open Access

Journal of Experimental & Clinical Cancer Research 1/2014

Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model

Zeitschrift:
Journal of Experimental & Clinical Cancer Research > Ausgabe 1/2014
Autoren:
Guo-Hua Deng, Jie Liu, Jie Zhang, Ying Wang, Xing-Chen Peng, Yu-Quan Wei, Yu Jiang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1756-9966-33-21) contains supplementary material, which is available to authorized users.

Competing interests

The authors declare no conflict of interests.

Authors’ contributions

YJ and YQW designed the procedure of the study. GHD carried out the plan and drafted the manuscript. JL, JZ and YW participated in cell culture, animal experiments and immunohistological analysis. XCP assisted in RT-PCR and statistical analysis. YJ and YQW supervised the whole experimental work and revised the manuscript. All authors read and approved the manuscript.

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.
Zusatzmaterial
Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 5
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Authors’ original file for figure 6
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Literatur
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