Tackling radioresistance of hypoxic cells by metabolic modulation of bioenergetics--a 31P MRS study on perfused Ehrlich ascites tumor cells.

ABSTRACT

In an attempt to overcome resistance of hypoxic cells to radiotherapy, the combination of a hematoporphyrin derivative (Hpd) and 2-deoxy-D-glucose (2-DG), a promising radiomodifier, was evaluated by assessing the alterations in phosphorylated metabolites and bioenergetics induced in perfused Ehrlich ascites tumor (EAT) cells, using Phosphorus-31 Magnetic Resonance Spectroscopy (31P-MRS). By reducing flow rate of perfusion, a relatively hypoxic condition of tumor was simulated. Changes in bioenergetics levels induced by the combined treatment of Photosan, a Hpd, and 2-DG, under reduced perfusion conditions were more pronounced. Significantly higher uptake of 2-DG and irreversibility of the reduction in cellular bioenergetics induced by the combined treatment, observed under simulated hypoxic conditions, might have considerable implications in optimizing tumor radiotherapy using 2-DG as an adjuvant. These result also suggest the usefulness of this technique to easily simulate hypoxic conditions of tumors in vitro that could be used for rapid in vitro pharmacological evaluation of promising therapeutic strategies.