Photodynamic therapy combined with temozolomide inhibits C6 glioma migration and invasion and promotes mitochondrial-associated apoptosis by inhibiting sodium-hydrogen exchanger isoform 1

Abstract Objective As a targeted therapeutic technique for gliomainhibition, photodynamic therapy (PDT) has gradually become a focus of basic research related to gliomatreatment. The capacity of PDT to kill gliomacells involves varieties of pathways. In gliomacells, activated sodium-hydrogen exchanger isoform 1 (NHE1) can inhibit the cytotoxic effect of temozolomide(TMZ), promote cell migration and invasion, and inhibit cell apoptosis by changing the acid-base equilibrium. The purpose of our study was to explore if PDT combined with TMZ can effectively inhibit gliomacells by influencing NHE1 in vitro. Methods We analyzed the expression levels of proteins such as NHE1, ezrin, vimentin, Bcl-2, and Bax by Western blot analysis, we assessed the migration and invasion of rat C6 gliomacells by Transwell assay, and we evaluated C6 cell apoptosis in vitro by flow cytometry. Results Western blot results indicated that NHE1, ezrinand vimentinwere downregulated after cotreatment of C6 cells, and intracellular acidification was detected by a fluorometric intracellular pHassay. The migration and invasion capacities of C6 cells were significantly hindered after cotreatment, as shown by the Transwell assay. Experimental data also revealed a significant increase in cell apoptosis after cotreatment, as detected by flow cytometry; corresponding proapoptotic changes in Bcl-2, Bax and caspase-3 were also observed in vitro. Conclusion These results demonstrate that PDT combined with TMZ can inhibit C6 cell migration and invasion and promote mitochondrial-associated apoptosis by inhibiting NHE1. Therefore, this study provides supporting evidence for a potential methodfor the treatment of glioma.