Antiangiogenic effect of propranolol on the growth of the neuroblastoma xenografts in nude mice

Background: Propranolol has been reported to display an antiangiogenic effect on infantile hemangiomas and also some adult cancers. Little is known, however, about whether propranolol has such effect on pediatric malignancies. Methods: Nude mice bearing BE(2) C neuroblastoma xenografts were injected intraperitoneally with propranolol and divided into groups of PROP-2 (n = 11), -5 (n = 11), and -10 (n = 10) according to the treating dosages of 2, 5, and 10 mg kg(-1) day(-1), respectively. The tumor volume and body weight were recorded every other day. All mice were sacrificed on day 9, and the levels of angiogenic factors were measured in harvested xenografts by immunohistochemistry and western blotting. Results: The tumor volume and weight of PROP-2 (0.72 +/- 0.28 cm(3), 0.59 +/- 0.21 g) and PROP-5 (0.81 +/- 0.35 cm(3), 0.61 +/- 0.25 g) were significantly decreased when compared with those of CTL (1.22 +/- 0.58 cm(3), 0.93 +/- 0.15 g; P < 0.01). The tumor microvessel density (MVD) scores that PROP-2, -5, and -10 groups had (49.28 + 17.53, 52.45 + 17.11, and 51.09 + 13.18 pixels per picture, respectively) were lower than those from the control group (65.29 +/- 17.33 pixels per picture, P < 0.01). Furthermore, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), and metalloproteinase-9 (MMP-9) levels were significantly lower in the groups with propranolol treated dosage of 5 and 10 mg kg(-1) day(-1) than in the control group. Conclusions: Propranolol can exhibit an inhibitory effect on the tumor growth and angiogenic factors expression in neuroblastoma xenografts, which may provide some knowledge to the role of beta-blockers in the management of NB. (c) 2013 Elsevier Inc. All rights reserved.