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The Role Of DNA Repair Protein RAD51 In The Therapy Of Osteosarcoma

Posted on:2010-09-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:L Q DuFull Text:PDF
GTID:1484303317950509Subject:Radiation Medicine
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Osteosarcoma is the most common non-hematological primary malignant tumors in children. Ionizing radiation (IR) or drug resistance is an underlying mechanism contributing to the failure of therapy in these patients. Therefore, the relationship between Rad51 protein in HR and IR or drug resistance was investigated in our research.It is not clear about Rad51 expression in osteosarcoma and the relationship between RAD51 expression and IR sensitivity or chemoresistance, although high expression of Rad51 is associated with enhanced resistance to DNA-damage induced by chemicals and/or ionizing radiation in several experimentsThrough immunohistochemical analysis of osteosarcoma specimens and adjacent osteosarcoma specimens, it was found that there is a high level expression of RAD51 protein in osteosarcoma cancer tissue regardless of histology or stage. In our experiments, there is a high level of RAD51 protein expression in all osteosarcoma cell lines, however, apparent difference between these cell lines was found too.It was observed that the changes of chemo- and radio- sensitivity of cultured osteosarcoma cell, the results indicated that there a negative correlation between RAD51 protein level and radiO- and chemo-sensitivity.RNAi technology is a new and powerful tool for researching gene function in recent years. We successfully constructed pGCshRNA-RAD51 vector, and got stable silencing of RAD51 gene of osteosarcoma cell lines by transfecting osteosarcoma cells HOS and selecting with G418.It was elucidated that the possibility of using Rad51 in the treatment of human osteosarcoma in vitro. It was analyzed that changes of chemo-and radiation sensitivity in cultured osteosarcoma cells after suppression of Rad51 expression. The results indicated that suppressed Rad51 could make cell cycle arrest in G2 phase, inhibit tumor cell proliferation. In conclusion, RAD51 might play an important role in radiation sensitivity and chemosensitivity of human osteosarcoma by augment the apoptosis.
Keywords/Search Tags:RAD51, Osteosarcoma, Radiosensitivity, Chemosensitivity, ProliferatlonjApoptosis, Cell cycle
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