Effect of talaporfin sodium-mediated photodynamic therapy on cell death modalities in human glioblastoma T98G cells.
Effect of talaporfin sodium-mediated photodynamic therapy on cell death modalities in human glioblastoma T98G cells.
复制标题
DOI：
10.2131/jts.39.821
复制
发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Y. Miki;J. Akimoto;Michika Hiranuma;Y. Fujiwara
中科院分区：
文献类型：
--
作者：
Y. Miki;J. Akimoto;Michika Hiranuma;Y. Fujiwara
虽然光动力疗法（PDT）是胶质瘤的有效治疗，但诱导胶质瘤细胞的凋亡性细胞死亡对于确保PDT治疗胶质瘤患者的有效性和安全性是重要的，因为坏死细胞死亡可诱导治疗中的晚期出现障碍。在这里，我们研究了细胞死亡的类型和PDT治疗条件涉及的激光和光敏剂剂量在人胶质母细胞瘤T98 G细胞之间的关系。光敏剂他拉泊芬钠介导的PDT（NPe 6-PDT）处理诱导T98 G细胞中激光和NPe 6剂量依赖性细胞死亡，而几乎所有用≥ 30 µg/mL NPe 6预处理的细胞都被激光照射杀死，无论激光剂量如何。形态学分析表明，高剂量NPe 6和激光照射的组合改变了主导细胞死亡过程从凋亡到坏死。生化分析（检测半胱天冬酶-3活性和染色细胞表面暴露的磷脂酰丝氨酸）也表明，增加激光剂量改变了细胞死亡的类型从凋亡到坏死性细胞死亡后，高剂量治疗NPe 6。乳酸脱氢酶渗漏试验表明，5 J/cm（2）的激光剂量诱导的渗漏小于30 J/cm（2）。我们的研究结果表明，NPe 6-PDT中胶质瘤细胞死亡的类型随着激光和NPe 6剂量的波动而变化，并且30 µg/mL NPe 6与5 J/cm（2）激光的组合是在体外研究中诱导凋亡细胞增加同时保持低坏死细胞死亡率的最佳治疗条件。
While photodynamic therapy (PDT) is an effective treatment for glioma, induction of apoptotic cell death of glioma cells is important for ensuring efficacy and safety of PDT treatment in glioma patients, as necrotic cell death can induce late appearance of obstacles in treatment. Here, we investigated the relationship between type of cell death and PDT treatment conditions involved in laser and photosensitizer dosage in human glioblastoma T98G cells. Photosensitizer talaporfin sodium-mediated PDT (NPe6-PDT) treatment induced laser and NPe6 dose-dependent cell death in T98G cells, whereas almost all cells pretreated with NPe6 at ≥ 30 µg/mL were killed by laser irradiation, regardless of laser dose. Morphological analysis showed that combination of high doses of NPe6 and laser irradiation changes the dominant cell death process from apoptosis to necrosis. Biochemical analysis (detection of caspase-3 activity and staining of cell surface-exposed phosphatidylserine) also showed that increasing laser dose changes the type of cell death from apoptotic to necrotic cell death after high-dose treatment with NPe6. Lactate dehydrogenase leakage assay demonstrated that a laser dose of 5 J/cm(2) induced less leakage than 30 J/cm(2). Our results suggested that type of glioma cell death in NPe6-PDT changed with fluctuations in laser and NPe6 dose, and that combination of 30 µg/mL NPe6 with 5 J/cm(2) laser is the best treatment condition for inducing an increase in apoptotic cells while keeping rate of necrotic cell death low in this in vitro study.