Study On The Radiosensitivity Evaluation Of Tumor Cells And The Radio-sensitization Of ANTP-Smac N7 Fusion Peptide

In the clinical practice of radiotherapy for tumor, we often discover that there is so much difference of therapeutic effects and the damage to the normal tissue around tumor among different patients who have different tumor or the different patho-type of the same tumor. The difference of radio-sensitivity in tumor cells is the main reason for this. We are effort to establish sensitive and rapid methods and biomarkers to predict the radio-sensitivity of tumor cells before the radiotherapy. Physicians can make different individual plan in their radiaotherapy for each patient according to the prediction of radio-sensitivity.We detect the deletion of mitochondrial DNA 4977bp (AmtDNA4977) using nest PCR and detect the DNA double-strand break (DNA-DSB) using single cell gel electrophoresis for tumor cells not only in vitro but also in vivo. The radio-sensitivity of tumor cells can be judged according to the quantity ofâ–³mtDNA4977 and DNA-DSB. The AmtDNA4977 and DNA-DSB in the tumor cells of patients were also detected using the same methods and we can make the judgement about the patients'radio-sensitivity. We can provide the economic and rapid methods and biomarkers for the prediction of radio-sensitivity according to the methods combined for the detection of AmtDNA4977 and DNA-DSB.Smac is a protein can promote apoptosis. Smac N7 is the active domain of smac protein which has the apoptosis-promoting function and it only work in the cells which have been damaged. High-expression of the inhibitor of apoptosis protein (IAPs) in the tumor cells can inhibit apoptosis and decrease the radio-sensitivity of tumor cells. Smac N7 can inhibit the active of IAPs because of the special binding to IAPs and then increase the radio-sensitivity of tumor cells. This is the advancing front nowadays in the area of radiation biology. However, the expression of Smac protein is very low in tumor cells which have radiation toleration and the exogenous Smac N7 can't enter the tumor cells. Therefore, we will transfer Smac N7 into the tumor cells and explore the mechanism of apoptosis-promoting in this study. ANTP is a membrane permeability peptide which has been discovered at the earlier time. We will link Smac N7 with ANTP to a fusion peptide and transfer Smac N7 into tumor cells by the membrane-permeability of ANTP that considered as leader peptide. We are effort to clear the mechanism for radio-sensitization of the fusion peptide by detecting the expression of XIAP and caspase induced by radiation when we transfer the fusion peptide into tumor cells. It may be great value in the exploring new drug for radio-sensitization and increase the effect of radiation therapy.