Radioresistance is associated to increased Hsp70 content in human glioblastoma cell lines.
Radiation therapy is routinely prescribed for high-grade malignant gliomas. However, the efficacy of this therapeutic modality is often limited by the occurrence of radioresistance, reflected as a diminished susceptibility of the irradiated cells to undergo apoptosis. Heat-shock proteins (Hsps) synthesis can be increased by cellular insults, such as radiation-induced damage. Inducible Hsp70 has been suggested to have multiple roles in cytoprotection against apoptosis. Accordingly, high levels of Hsp70 prevent stress-induced apoptosis. In the present study, we investigated whether the content of Hsp70 is associated to glioblastoma cell radioresistance. To this end, the U-87MG, U-251MG and MO59J human glioblastoma cell lines were irradiated at 2, 5 and 10 Gy and their relative radioresistance and Hsp70 were determined. Following 5 Gy irradiation, in MO59J and U-251MG a significant decrease in colony formation was found, whereas the U-87MG was relatively radioresistant. Three hours after the irradiation (at 5 Gy) Hsp70 contents increased 110% in the U-87 MG cells, but did not significantly change in the U-251MG and MO59J cells. Thus, our results suggest that Hsp70 protection against radiation-induced apoptosis might underlie glioblastoma radioresistance.
South-American Office for Anticancer Drug Development (SOAD), Rua Ramiro Barcelos 2350, 3 andar, Porto Alegre. brondani@terra.com.br
Adriana
A
Brondani Da Rocha
Andrea
A
Regner
Ivana
I
Grivicich
Daniel
D
Pretto Schunemann
Celito
C
Diel
Giovana
G
Kovaleski
Caroline
C
Brunetto De Farias
Edlaine
E
Mondadori
Leonardo
L
Almeida
Aroldo
A
Braga Filho
Gilberto
G
Schwartsmann
D017209:Apoptosis; D002453:Cell Cycle / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D011836:Radiation Tolerance / Q000502:physiology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018840:HSP70 Heat-Shock Proteins