Response of breast cancer carcinoma spheroids to combination therapy with radiation and DNA-PK inhibitor: growth arrest without a change in α/ß ratio.
Int J Radiat Biol
; 96(12): 1534-1540, 2020 12.
Article
de En
| MEDLINE
| ID: mdl-33074046
ABSTRACT
PURPOSE:
Agents that increase tumor radiosensitivity are of interest in improving outcomes in radiotherapy (XRT). DNA-PK inhibitors radiosensitize and alter cell adhesion proteins. We investigated combination radiation and a DNA-PK inhibitor in monolayers vs spheroids. MATERIALS ANDMETHODS:
Using HER2 positive mammary carcinoma cells, we investigated the impact of NU7441, a DNA-PK inhibitor, on irradiated monolayer and spheroid cultures. Colony formation assays were performed with monolayer culture cells and spheroids after irradiation with/without NU7441 (5 µM).RESULTS:
In monolayer culture cells, α/ß increased from 3.0 ± 0.2 Gy (XRT alone) to 6.9 ± 0.2 Gy (XRT+NU7441). Corresponding α/ß values for cells obtained by disaggregating treated spheroids were 3.6 ± 0.7 Gy (XRT alone) and 3.5 ± 0.2 Gy (XRT+NU7441). However, spheroid survival was highly sensitive to NU7441 incubation. After 4 Gy XRT alone 75% of the irradiated spheroids remained intact; when NU7441 treatment was involved, 13% remained intact. No spheroids survived to 3 weeks at 6 Gy or more. The discrepancy between the minimal change in α/ß from cells derived from spheroids and the spheroid growth response was not related to poor penetration of NU7441.CONCLUSIONS:
DNA-PK inhibitor NU7441 radiosensitized monolayer cells but not cells obtained from spheroids. NU7441 and radiation increased spheroid fragmentation.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du sein
/
Sphéroïdes de cellules
/
Inhibiteurs de protéines kinases
/
DNA-activated protein kinase
Limites:
Humans
Langue:
En
Journal:
Int J Radiat Biol
Sujet du journal:
RADIOLOGIA
Année:
2020
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique