Modulation of response to radiation of human lung cancer cells following insulin-like growth factor 1 receptor inactivation.
Targeted disruption of the insulin-like growth factor 1 receptor (IGF-1R) restricts proliferation of tumor cells and enhances their in vitro radiosensitivity. However, there is little information regarding the effect of IGF-1R expression and function on the lung cancer response to radiotherapy. In this study, we evaluated the cell surface expression of IGF-1R and the antitumoral effect of IGF-1R blockade in combination with irradiation in 6 non-small cell lung cancer (NSCLC) cell lines. All cell lines showed specific IGF-1 binding with an affinity ranging from 0.95x10(-9) to 2.3x10(-9) M, which was evaluated by competitive binding assay. The amount of binding sites ranged from 118 to 377 fmol/mg protein. In one cell line (U1810), the combined treatment led to synergistic cell death and was associated with an accumulation of cells in the G2 phase. IGF-1R activation was able to obstruct serum starvation/radiation-induced cell death in U1810 cell line. Additive interactions were found for four cell lines (A549, H157, H23 and H125) whereas only subadditive effects were observed in U1752 cell line. Our results indicate that the IGF-1R is present on NSCLC cells and thereby its involvement in the modulation of radiosensitivity in lung cancer cells.
Cosaceanu
Daria
D
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute/Hospital, R8:00, Stockholm S-171 76, Sweden.
Carapancea
Mia
M
Castro
Juan
J
Ekedahl
Jessica
J
Kanter
Lena
L
Lewensohn
Rolf
R
Dricu
Anica
A
D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000528:radiation effects; D016923:Cell Death; D005786:Gene Expression Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis* / Q000502:physiology*
D017526:Receptor, IGF Type 1