title: Exogenous norepinephrine attenuates the efficacy of sunitinib in a mouse cancer model.
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.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Deng
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Peng
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
authors.affiliation: Cancer Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan Province 610041, China. jiangyu1973@hotmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007211:Indoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011758:Pyrroles / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D015398:Signal Transduction; D000077210:Sunitinib; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D020533:Angiogenesis Inhibitors; D007211:Indoles; D015850:Interleukin-6; D016209:Interleukin-8; D011758:Pyrroles; D011943:Receptors, Adrenergic, beta; D042461:Vascular Endothelial Growth Factor A; D011433:Propranolol; D000077210:Sunitinib; D009638:Norepinephrine