Low-dose arsenic trioxide enhances 5-aminolevulinic acid-induced PpIX accumulation and efficacy of photodynamic therapy in human glioma
Low-dose arsenic trioxide enhances 5-aminolevulinic acid-induced PpIX accumulation and efficacy of photodynamic therapy in human glioma
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低剂量三氧化二砷增强 5-氨基乙酰丙酸诱导的 PpIX 积累和光动力疗法在人胶质瘤中的疗效
DOI：
10.1016/j.jphotobiol.2013.06.001
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发表时间：
2013-10-05
影响因子：
5.4
通讯作者：
Zhao, Shiguang
中科院分区：
文献类型：
--
作者：
Wang, Chunlei;Chen, Xiaofeng;Zhao, Shiguang
在胶质瘤治疗策略中，基于5-氨基乙酰丙酸（5-ALA）的荧光引导切除术（FGR）和光动力疗法（PDT）已被用作治疗恶性胶质瘤的有效新方法。然而，细胞内原卟啉IX（PpIX）积累不足限制了FGR和PDT在胶质瘤边缘区域的应用。为了克服这些问题，我们评估了细胞内水平的PpIX在人胶质瘤细胞系和大鼠皮质星形胶质细胞预处理0.1 μ M三氧化二砷（ATO）。采用Annexin V-FITC凋亡检测试剂盒和MTT法分别检测PDT后细胞凋亡和细胞活力。为了寻找可能的机制，我们研究了在胶质瘤细胞中血红素生物合成途径中调节卟啉合成的关键酶的表达。我们的研究结果表明，5-ALA诱导的PpIX积累在胶质瘤细胞系预处理0.1 μ M ATO相对于对照组增加。在使用相同浓度的ATO预处理的大鼠皮质星形胶质细胞中未检测到荧光强度的变化。0.1 μ M ATO预处理的胶质瘤细胞PDT后的凋亡率明显高于对照组，尤其是晚期凋亡细胞，而细胞活力降低。用0.1 μ M ATO预处理后，胶质瘤细胞中CPOX的表达上调。我们得出的结论是，ATO是增强细胞内PpIX积累并改善5-ALA诱导的FGR和PDT在胶质瘤中的益处的潜在可选方法。(C)2013年由Elsevier B. V.出版
Among glioma treatment strategies, 5-aminolevulinic acid (5-ALA)-based fluorescence-guided resection (FGR) and photodynamic therapy (PDT) have been used as effective novel approaches against malignant glioma. However, insufficient intracellular protoporphyrin IX (PpIX) accumulation limits the application of FGR and PDT in the marginal areas of gliomas. To overcome these issues, we assessed the intracellular levels of PpIX in human glioma cell lines and rat cortical astrocytes pretreated with 0.1 mu M arsenic trioxide (ATO). Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay, respectively. In order to find out the possible mechanism, we investigated the expression of the key enzymes in the heme biosynthesis pathway, which regulates porphyrin synthesis in glioma cells. Our findings showed that the 5-ALA-induced PpIX accumulation in glioma cell lines pretreated with 0.1 mu M ATO was increased relative to the control groups. No changes in fluorescence intensity were detected in the rat cortical astrocytes pretreated using the same ATO concentration. Apoptosis following PDT in glioma cells pretreated with 0.1 mu M ATO were significantly higher than in control groups, especially late apoptotic cells, while the cell viability was decreased. The expression of CPOX was upregulated in glioma cells after pretreatment with 0.1 mu M ATO. We concluded that ATO was a potential optional approach in enhancing intracellular PpIX accumulation and improving the benefits of 5-ALA-induced FGR and PDT in glioma. (C) 2013 Published by Elsevier B.V.