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 β-blockers in the management of NB.
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 β-blockers in the management of NB.
Authors: Gauthier Bouche; Nicolas André; Shripad Banavali; Frank Berthold; Alfredo Berruti; Guido Bocci; Giovanni Brandi; Ugo Cavallaro; Saviero Cinieri; Marco Colleoni; Giuseppe Curigliano; Teresa Di Desidero; Alexandru Eniu; Nicola Fazio; Robert Kerbel; Lisa Hutchinson; Urszula Ledzewicz; Elisabetta Munzone; Eddy Pasquier; O Graciela Scharovsky; Yuval Shaked; Jaroslav Stěrba; Martin Villalba; Francesco Bertolini Journal: Ecancermedicalscience Date: 2014-09-09