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

• Published in: Lasers in surgery and medicine 2014-07, Vol.46 (5), p.422-430
• Main Authors: Zhang, Xufeng, Cong, Damin, Shen, Dawei, Gao, Xin, Chen, Lei, Hu, Shaoshan
• Format: Article
• Language: English
• Subjects: Animals; Biomarkers - metabolism; Brain Neoplasms - drug therapy; bumetanide; Bumetanide - therapeutic use; Cell Line, Tumor; Diuretics - therapeutic use; Edema - chemically induced; Edema - drug therapy; Edema - metabolism; Glioma - drug therapy; hematoporphyrin monomethyl ether; Hematoporphyrins - adverse effects; Hematoporphyrins - therapeutic use; Male; microvessel density; NKCC-1; peri-tumor edema; Photochemotherapy - adverse effects; photodynamic therapy; Photosensitizing Agents - adverse effects; Photosensitizing Agents - therapeutic use; Random Allocation; Rats; Rats, Wistar; Transplantation, Heterologous; Treatment Outcome; Zonula occludens-1 (ZO-1)
• ISSN: 0196-8092; 1096-9101
• DOI: 10.1002/lsm.22248

Objective The aim of this study was to investigate the effect of bumetanide on 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 hematoporphyrin monomethyl ether (HMME)‐mediated PDT, injection of bumetanide or 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. Bumetanide enhanced the efficacy of PDT and reduced PDT‐induced peri‐tumor edema in the combined PDT + bumetanide treatment 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 + bumetanide treatment group. Conclusion PDT, in combination with bumetanide was 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.