The effect of bumetanide on photodynamic therapy‐induced peri‐tumor edema of C6 glioma xenografts

Objective The aim of this study was to investigate the effect of bumetanideon peri-tumor edema caused by photodynamic therapy (PDT) of intraparenchymal C6 glioma xenografts. Methods Seven days after inoculation with C6 cells, rats with MRI-confirmed glioma received hematoporphyrinmonomethyl ether (HMME)-mediated PDT, injection of bumetanideor a combination of the two treatments. After treatment, tumor volume, tumor weight, brain water content, microvessel density, expression of NKCC-1, Zonula occludens-1 (ZO-1), and animal survival time were examined. Results In the PDT group, tumor growth was significantly inhibited and survival prolonged. Bumetanideenhanced the efficacy of PDT and reduced PDT-induced peri-tumor edema in the combined PDT +  bumetanidetreatment group where NKCC-1 expression in response to PDT was significantly suppressed. ZO-1 expression was significantly suppressed in the PDT-only group. This suppression was not observed in the combined PDT +  bumetanidetreatment group. Conclusion PDT, in combination with bumetanidewas seen to significantly inhibit the growth of C6 glioma, relieve peri-tumor edema caused by PDT alone and prolong survival. These results suggest that PDT, in combination with bumetanide, may be a useful and promising strategy in the treatment of human glioma. Lasers Surg. Med. 46:422–430, 2014. © 2014 Wiley Periodicals, Inc.