2. Academic Validation
  3. A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation

A novel tumor spheroid model identifies selective enhancement of radiation by an inhibitor of oxidative phosphorylation

  • Oncotarget. 2019 Sep 3;10(51):5372-5382. doi: 10.18632/oncotarget.27166.
Henning Karlsson 1,  Wojciech Senkowski 1,  Mårten Fryknäs 1,  Sharmineh Mansoori 1,  Stig Linder 2 3,  Joachim Gullbo 4,  Rolf Larsson 1,  Peter Nygren 4
Affiliations

Affiliations

  • 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.
PMID: 31523395 DOI: 10.18632/oncotarget.27166
Abstract

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.

Keywords

high-throughput; hypoxia; radiosensitizer; spheroid; tumor model.

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