Intestinal Absorption ; Schistosomicides/*metabolism ; Solubility

Objective:To comparison of three different beta blockers on murine hemangioma (EOMA cells) cells in vitro and in vivo effects.Preliminary study on the therapeutic effect of propranolol on vascular tumor in mice and possible mechanisms , provide a reference for beta blockers in the treatment of infantile hemangioma .Methods: Comparative study on the effects of three kinds of different β-receptor blockers---metoprolol, propranolol and butoxamine , on the proliferation and apoptosis of Mouse Hemangioendothelioma Endothelial cell (EOMA cells) was conducted in vitro.EOMA cells were cultured in vitro,randomly divided into different groups,propranolol and timolol were added into the medium respectively ,after 24 h intervention.MTT assay and acridine orange staining assay were conducted respectively to detect cell viability and apoptosis level .EOMA cells were transplanted into nude mice in vivo.Tumor volume growth to 100 mm3 ,animals were randomly divided into 4 groups respectively ,the control group ,metoprolol group,Bhutto Samin group and propranolol group ,drug group according to 2 mg/( kg? d) oral gavage ,control group were given an equal volume of saline ( NS ) , every two days measurement tumor volume size .Serum levels of tumor necrosis factor alpha ( TNF-α) and vascular endothelial growth factor ( VEGF ) were detected by enzyme linked immunosorbent assay ( ELISA ) in the end of the experiment.Results:For propranolol,after 24 h treatment,significant differences of cell viability and apoptosis were noted (P<0.05) at the concentration of 50 μmol/L,while continuing to increase to 800 μmol/L,the cell survival rate decreased sharply to close to 10%. Acridine orange staining at the 50 μmol/L group after 24 h revealed many apoptotic cells .For metoprolol and butoxa mine ,significant differences of cell viability and apoptosis were noted ( P<0.05 ) at the concentration of 100 μmol/L,while continuing to increase to 800μmol/L,the cell survival rate decreased sharply to close to 20%.It was significantly higher than propranolol group at the same concentration ( P<0.05 ) .It showed a similar trend in acridine orange staining .In vivo experiments showed that the end of the experiment of metoprolol , butoxamine group and propranolol drugs in mice tumor volume , respectively ( 1 642.8 ±89.3 ) , ( 1 529.3 ± 119.1) and (752.7±46.5)mm3,significantly lower than the control group of mice tumor volume of (2 023.3±123.0) mm3(P<0.001).Metoprolol,butoxamine mice and propranolol drugs group ,serum VEGF levels for (606.5±105.8 ) pg/ml,(534.3±243.2 ) pg/ml and (420.1±123.7) pg/ml, significantly lower than the PBS control group [(825.8±145.7) pg/ml,(P<0.05)],the TNF alpha result was followed by(301.3±62.3) pg/ml,(305.1±53.8) pg/ml and (288.8±59.5) pg/ml,significantly lower than the normal control group [(444±100.4) pg/ml,P<0.05].Conclusion:Three kinds of beta-blockers can effectively inhibit EOMA cells proliferation and induce apoptosis in vitro, the role of propranolol more significantly than butoxamine and metoprolol .Three kinds of beta blockers restrain the growth of the hemangioma in vivo ,in which the inhibitory effect of propranolol is stronger than the metoprolol and butoxa mine.Three kinds of beta blockers can lower the levels of VEGF and TNF-αin vivo.Indicating that propranolol on vascular tumor in mice may be one of the mechanisms of β1 and β2 receptor synergy effect and its mechanism in the treatment of hemangioma may be associated with VEGF and TNF-α.