Underlying mechanism of the photodynamic activity of hematoporphyrin­induced apoptosis in U87 glioma cells.

Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method with low toxicity and limited side­effects. The aim of the present study was to investigate the underlying mechanism and potential microRNAs (miRNAs) involved in the treatment of glioma by PDT with hematoporphyrin, a clinical photosensitizer. The photodynamic activity of hematoporphyrin on the cell viability and apoptosis of gliomas was investigated by MTT, and flow cytometry and fluorescence microscopy, respectively. Alterations in singlet oxygen and mitochondrial membrane potential were detected. The differentially expressed miRNAs and proteins were evaluated by miRNA gene chip and apoptosis­associated protein chip, respectively. The results demonstrated that cell viability significantly decreased with hematoporphyrin concentration. PDT with hematoporphyrin significantly increased cell apoptosis at a later stage, induced the content of reactive oxygen species (ROS) and decreased the mitochondrial membrane potential, indicating that PDT with hematoporphyrin inhibited cell growth via induction of radical oxygen, decreased the mitochondrial membrane potential and induced apoptosis. The upregulated miRNAs, including hsa­miR­7641, hsa­miR­9500, hsa­miR­4459, hsa­miR­21­5p, hsa­miR­663a and hsa­miR­205­5p may be important in PDT­induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B member­ and nuclear factor­κB­mediated apoptosis signaling pathways were the most significant pathways. Thus, the current study presents PDT as a potential therapeutic approach for the treatment of malignant glioma, and identified miRNAs for the molecular design and development of a third­generation photosensitizer (PS).