Anti-MDM2 (aa 104-157) polyclonal antibody

Biological experiments clarify that p53-Mdm2 module is the core of tumor network and p53 oscillation plays an important role in determining the tumor cell fate. In this paper, we investigate the effect of time delay on the oscillatory behavior induced by Hopf bifurcation in p53-Mdm2 system. First, the stability of the unique positive equilibrium point and the existence of Hopf bifurcation are investigated by using the time delay as the bifurcation parameter and by applying the bifurcation theory. Second, the explicit criteria determining the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are developed based on the normal form theory and the center manifold theorem. In addition, the combination of numerical simulation results and theoretical calculation results indicates that time delays in p53-Mdm2 system are critical for p53 oscillations. The results may help us to better understand the biological functions of p53 pathway and provide clues for treatment of cancer.

Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro-architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti-cancer, anti-inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K-AKT-NFATc1 pathway is one of the most important downstream pathways of RANKL-induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K-AKT-NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM-p53-induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy-induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti-cancer drug triptolide was demonstrated to be anti-osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.