Effect of propranolol on IL-10, visfatin, Hsp70, iNOS, TLR2, and survivin in amelioration of tumor progression and survival in Solid Ehrlich Carcinoma-bearing mice

Pharmacol Rep. 2014 Dec;66(6):1114-21. doi: 10.1016/j.pharep.2014.07.010. Epub 2014 Aug 8.


Background: β-Adrenergic signaling could contribute to initiation and progression of breast cancer. This research investigated some potential mechanisms of propranolol in amelioration of progression and survival in breast cancer.

Methods and results: Solid Ehrlich Carcinoma (SEC) xenograft model was induced in 30 mice divided into 3 groups; where group I served as untreated SEC group. In groups II and III, propranolol treatment i.p. in low (5mg/kg) and high dose (10mg/kg) caused significant increase in interleukin-10 (IL-10) and decrease in heat shock protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) activity with non significant change in visfatin in tumor tissues compared to untreated SEC. In untreated SEC, tumor volume (V) exhibited significant negative correlation with IL-10 levels and toll like receptor 2 (TLR2) expression with significant positive correlation with Hsp70 levels and iNOS activity. While propranolol in either doses caused reduction of tumor volume (V), and improved percentage tumor growth inhibition (% TGI) only its high dose exhibited significant impact on survival rate. Propranolol dose-dependent effect was evident for IL-10 and Hsp70, and even only the high dose significantly increased and decreased TLR2 and survivin, respectively. This comes in favor of recommending high dose of propranolol in cancer therapy. Nonetheless, use of low dose cannot be ignored when benefit to risk balance have to be considered.

Conclusions: Propranolol could provide palliative effects in progression and survival of breast cancer that are mainly mediated via direct immunomodulatory and apoptotic mechanisms and probably associated with indirect anti-angiogenic activity.

Keywords: Angiogenesis; Apoptosis; Immunomodulation; Propranolol; Solid Ehrlich Carcinoma.

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy
  • Carcinoma, Ehrlich Tumor / drug therapy*
  • Carcinoma, Ehrlich Tumor / pathology
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • HSP70 Heat-Shock Proteins / metabolism
  • Inhibitor of Apoptosis Proteins / metabolism
  • Interleukin-10 / metabolism
  • Mice
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Propranolol / administration & dosage
  • Propranolol / pharmacology*
  • Repressor Proteins / metabolism
  • Survival Rate
  • Survivin
  • Toll-Like Receptor 2 / metabolism
  • Xenograft Model Antitumor Assays


  • Adrenergic beta-Antagonists
  • Birc5 protein, mouse
  • HSP70 Heat-Shock Proteins
  • Inhibitor of Apoptosis Proteins
  • Repressor Proteins
  • Survivin
  • Toll-Like Receptor 2
  • Interleukin-10
  • Propranolol
  • Nitric Oxide Synthase Type II
  • Nicotinamide Phosphoribosyltransferase