Objective　To compare the irradiation-protective and inter-synergestic effects of E838,WR-2721, Rubia cordifolia, cystamin e hydrochloride and ethinyl estradiol on radiation and combined radiation-burn injury. Methods　Above-mentioned drugs were given to the mice i ntraperitoneally, or intragastrcally, then, the mortality and the average surviv al d for 30 d were observed before and after the administration of the drug s. Results　①When drugs were before injury , the survival rate and the average survival d of the radiation and combined radiation-burn injured mice were increased obviously with the best effect in E838 and WR-2721. ②When drugs were given after injury, E838 and R. cordifolia also kept the effect. ③Combined appling WR-2721（pre) and E838（post）displayed a significant syner gistic reaction. Conclusion　E838 and WR-2721 are more e ffective than the others in the prevention of radiation.

OBJECTIVETo examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis.

METHODSThe osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 μmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-β1 (TGF-β1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay.

RESULTSCompared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-β1, NF-κB and Hes1 (P<0.05 or P<0.01).

CONCLUSIONBrucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Animals ; Bone Neoplasms ; metabolism ; prevention & control ; secondary ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; Cell Differentiation ; drug effects ; Cells, Cultured ; Female ; Humans ; Jagged-1 Protein ; metabolism ; Macrophages ; drug effects ; physiology ; Mice ; Osteoclasts ; drug effects ; physiology ; Receptor, Notch1 ; metabolism ; Signal Transduction ; drug effects ; Strychnine ; analogs & derivatives ; pharmacology ; therapeutic use