A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation
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Henning Karlsson1, Wojciech Senkowski1, Mårten Fryknäs1, Sharmineh Mansoori1, Stig Linder2,3, Joachim Gullbo4, Rolf Larsson1 and Peter Nygren4
1 Department of Medical Sciences, Uppsala University, Uppsala, Sweden
2 Department of Medical and Health Sciences, Linköping University, Linköping, Sweden
3 Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
4 Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Keywords: spheroid; tumor model; high-throughput; radiosensitizer; hypoxia
Received: February 18, 2019 Accepted: July 30, 2019 Published: September 03, 2019
There is a need for preclinical models that can enable identification of novel radiosensitizing drugs in clinically relevant high-throughput experiments. We used a new high-throughput compatible total cell kill spheroid assay to study the interaction between drugs and radiation in order to identify compounds with radiosensitizing activity. Experimental drugs were compared to known radiosensitizers and cytotoxic drugs clinically used in combination with radiotherapy. VLX600, a novel iron-chelating inhibitor of oxidative phosphorylation, potentiated the effect of radiation in tumor spheroids in a synergistic manner. This effect was specific to spheroids and not observed in monolayer cell cultures. In conclusion, the total cell kill spheroid assay is a feasible high-throughput method in the search for novel radiosensitizers. VLX600 shows encouraging characteristics for development as a novel radiosensitizer.
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