| AIM: Overexpression of the tyrosine kinase level of epidermal growth factor receptor (EGFR,ErbB) family members caused human carcinomas.Upon binding to specific ligands, the ErbB receptors dimerize and then activate downstream signal transduction pathways that regulate multiple biological processes including cell proliferation, differentiation and migration. Aberrant ErbB receptor singals usually contribute to the progression and development of a number of human malignant tumors. Our study is to screen the Sequence -dependent effect of Mabs C225 in combination with cytotoxic drugs's mechanisms, to find the best combination way and to provide a rationale for future clinical trials .METHODS: 1.MTT to conclude different drugs IC50(median effect), and calculated CI(combination index) analysis .2. Western blot analysis was used to determine protein changes after by different sequences of administration and same sequences of administrati . include (AKT,P-AKT,MAPK,P-MAPK).3.flow cytometric analysis of different sequences of administration and the same sequences of administrati effects on cell cycle distribution and cell death.RESLUTS: 1. Different sequences of administration is better than the same sequences of administrati effects on kill cancer cell lines,different sequences of administration is better than the same sequences of administrati effects on CI ,CI value between 1 and 0.7 indicate slight synergism; 2. The Sequence -dependent effect of Mabs C225 in combination with cytotoxic drugs inhibited the phosphorylation of Akt and MAPK protein, which in turn led to the decreased phosphorylation .3. Cytotoxic drugs followed by Mabs C225 than the same sequences of administrati can make more cell death and G1/M were arrest.CONCLUSION: 1.the Sequence -dependent effect of Mabs C225 in combination with cytotoxic drugs inhibited the phosphorylation of Akt and MAPK protein, which in turn led to the decreased phosphorylation and cell death and Gl/M were arrest more better than same-time effect of Mabs C225 in combination with cytotoxic drugs,and the greatest level of synergism was obtained.2. We demonstrated that C225 is an effective anticancer as an various small molecule inhibitors of EGFR-TK enzymatic activity. 3.Mabs C225 has shown a synergistic effect with cytotoxic drugs... |
