Artículos de revistas
Inhibiting DNA-PKCS radiosensitizes human osteosarcoma cells
Fecha
2017Registro en:
Biochemical and Biophysical Research Communications, Volumen 486, Issue 2, 2018, Pages 307-313
10902104
0006291X
10.1016/j.bbrc.2017.03.033
Autor
Mamo, Tewodros
Mladek, Ann C.
Shogren, Kris L.
Gustafson, Carl
Gupta, Shiv K.
Riester, Scott M.
Maran, Avudaiappan
Galindo, Mario A.
van Wijnen, Andre J.
Sarkaria, Jann N.
Yaszemski, Michael J.
Institución
Resumen
© 2017 Elsevier Inc. Osteosarcoma survival rate has not improved over the past three decades, and the debilitating side effects of the surgical treatment suggest the need for alternative local control approaches. Radiotherapy is largely ineffective in osteosarcoma, indicating a potential role for radiosensitizers. Blocking DNA repair, particularly by inhibiting the catalytic subunit of DNA-dependent protein kinase (DNA-PKCS), is an attractive option for the radiosensitization of osteosarcoma. In this study, the expression of DNA-PKCS in osteosarcoma tissue specimens and cell lines was examined. Moreover, the small molecule DNA-PKCS inhibitor, KU60648, was investigated as a radiosensitizing strategy for osteosarcoma cells in vitro. DNA-PKCS was consistently expressed in the osteosarcoma tissue specimens and cell lines studied. Additionally, KU60648 effectively sensitized two of those osteosarcoma cell lines (143B cells by 1.5-fold and U2OS cells by 2.5-fold). KU60648 co-treatment also a