Effect of photodynamic therapy combined with torasemide on the expression of matrix metalloproteinase 2 and sodium-potassium-chloride cotransporter 1 in rat peritumoral edema and glioma.

Abstract

Peritumoral edema is a key stage in the infiltration and recurrence of glioma. Photodynamic therapy (PDT) increases the extent of peritumoral edema, which leads to a decrease in the effectiveness of PDT in treating glioma. The present study evaluated the effects of PDT combined with torasemide on the levels of matrix metalloproteinase (MMP) 2 and sodium-potassium-chloride cotransporter (NKCC) 1 in peritumoral edema regions of rat glioma. Adult male Wistar rats were inoculated with rat glioma C6 cells, and the presence of glioma was confirmed using magnetic resonance imaging 7 days subsequent to injection. The rats were randomly assigned to 4 groups (n=15): Control group, the rats received no treatment; PDT group, the rats received PDT at 80 J/cm2 for 10 min; torasemide group, the rats received 5 mg/kg torasemide intraperitoneally; and PDT + torasemide group, the rats received 5 mg/kg torasemide intraperitoneally for 3 days following PDT at 80 J/cm2 for 10 min. A total of 5 rats from each group were sacrificed 21 days following injection and the peritumoral edema tissues were harvested. MMP2 and NKCC1 expression levels were detected in the tissues using immunohistochemistry and western blot analysis. The mRNA expression levels of MMP2 and NKCC1 were observed using reverse transcription-quantitative polymerase chain reaction. Peritumoral edema was measured using a wet-to-dry weight (W/D) ratio, and survival times of the remaining 10 rats in each group were evaluated. Compared with the control group, tumor growth was significantly suppressed in the PDT group and the survival time was prolonged through a reduction in the expression of MMP2 (P<0.05), and an increased W/D ratio resulted in significantly increased expression of NKCC1 (P<0.05). Compared with the PDT group, the expression of NKCC1 and the W/D ratio in the PDT + torasemide group were significantly decreased (P<0.05), while no significant difference was observed in the expression levels of MMP2. In conclusion, PDT combined with torasemide prolonged the survival time of rats by inhibiting the growth of glioma through a reduction in the expression of MMP2, and by reducing peritumoral edema through a reduction in the expression levels of NKCC1.