The First Clinical Medical College, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
Department of Neurosurgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Int J Mol Med. 2018 Apr;41(4):2288-2296. doi: 10.3892/ijmm.2018.3400. Epub 2018 Jan 18.
Photodynamic therapy (PDT) is a relatively novel type of tumor therapy method with low toxicity and limited side‑effects. 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 apoptosis‑associated 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 hsa‑miR‑7641, hsa‑miR‑9500, hsa‑miR‑4459, hsa‑miR‑21‑5p, hsa‑miR‑663a and hsa‑miR‑205‑5p may be important in PDT‑induced cell apoptosis in glioma. Transporter 1, ATP binding cassette subfamily B member‑ and nuclear factor‑κB‑mediated 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 third‑generation photosensitizer (PS).
光动力疗法（PDT）是一种相对新颖的肿瘤治疗方法，具有低毒性和有限的副作用。本研究旨在探讨血卟啉作为临床光敏剂治疗脑胶质瘤的潜在机制和相关微小 RNA（miRNA）。通过 MTT、流式细胞术和荧光显微镜分别研究血卟啉对胶质瘤细胞活力和凋亡的光动力活性。检测单线态氧和线粒体膜电位的变化。通过 miRNA 基因芯片和凋亡相关蛋白芯片分别评估差异表达的 miRNA 和蛋白质。结果表明，细胞活力随血卟啉浓度的增加而显著降低。血卟啉 PDT 在后期显著增加细胞凋亡，诱导活性氧（ROS）含量降低，线粒体膜电位降低，表明血卟啉 PDT 通过诱导自由基氧抑制细胞生长，降低线粒体膜电位并诱导细胞凋亡。上调的 miRNA，包括 hsa-miR-7641、hsa-miR-9500、hsa-miR-4459、hsa-miR-21-5p、hsa-miR-663a 和 hsa-miR-205-5p，可能在 PDT 诱导的脑胶质瘤细胞凋亡中起重要作用。转运蛋白 1、ATP 结合盒亚家族 B 成员和核因子-κB 介导的凋亡信号通路是最显著的通路。因此，本研究提出 PDT 是治疗恶性脑胶质瘤的一种潜在治疗方法，并鉴定了 miRNA 用于第三代光敏剂（PS）的分子设计和开发。
