Knockdown of Rad51 expression induces radiation- and chemo-sensitivity in osteosarcoma cells.
Osteosarcoma is the common primary bone malignancy in children and young adults in Eastern countries. Resistance to ionizing radiation (IR) or drugs is an underlying mechanism contributing to the failure of therapy in these patients. Rad51 is the key protein of DNA homologous recombination repair. Although high expression of Rad51 is associated with enhanced resistance to DNA damage induced by chemicals and/or ionizing radiation, the relevance of Rad51 expression in osteosarcoma and its relationship with IR sensitivity and chemo-resistance is not well understood. In this study, we elucidated the possibility of using Rad51 in the treatment of human osteosarcoma in vitro. Changes in chemo- and radiation sensitivity in cultured osteosarcoma cells occurred after suppression of Rad51 expression, using a plasmid vector-mediated short hairpin RNA (shRNA) expression system. The suppression of Rad51 correlated with cell cycle arrest in the G2 phase and inhibited tumor cell proliferation. Our results suggest that Rad51 expression levels might play an important role in radiation- and chemo-sensitivity of human osteosarcoma.
Du
Li-Qing
LQ
Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union, Medical College, Tianjin Key Laboratory of Molecular Nuclear Medicine, Tianjin, 300192, China.
Wang
Yong
Y
Wang
Hong
H
Cao
Jia
J
Liu
Qiang
Q
Fan
Fei-Yue
FY
D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002469:Cell Separation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase / Q000096:biosynthesis / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D014183:Transplantation, Heterologous
D034741:RNA, Small Interfering; C495153:RAD51 protein, human; D051135:Rad51 Recombinase