Calcitriol enhances 5-aminolevulinic acid-induced fluorescence and the effect of photodynamic therapy in human glioma
Calcitriol enhances 5-aminolevulinic acid-induced fluorescence and the effect of photodynamic therapy in human glioma
复制标题
骨化三醇增强5-氨基乙酰丙酸诱导的荧光和光动力治疗人胶质瘤的效果
DOI：
10.3109/0284186x.2013.819993
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发表时间：
2014-03-01
期刊：
影响因子：
3.1
通讯作者：
Zhao, Shiguang
中科院分区：
文献类型：
--
作者：
Chen, Xiaofeng;Wang, Chunlei;Zhao, Shiguang
抽象背景。由于残留的浸润性胶质瘤细胞，胶质瘤复发经常发生在手术腔的边缘区域附近。脑胶质瘤切除术中使用5-氨基乙酰丙酸（ALA）作为一种有效的治疗方法，以区分恶性组织和脑组织，并促进患者的预后。基于ALA的光动力疗法是胶质瘤的有效辅助治疗方式。然而，不足的原卟啉IX（PpIX）的积累可能会限制荧光引导切除术和光动力疗法在胶质瘤的边缘区域的适用性。方法.为了能够理解如何克服这些问题，使用人神经胶质瘤细胞和正常星形胶质细胞作为模型系统。胶质瘤细胞和星形胶质细胞用骨化三醇预处理48小时，然后用ALA孵育。评估光暴露后ALA诱导的PpIX荧光和细胞存活的变化。此外，卟啉合成酶在预处理的胶质瘤细胞中的表达进行了分析。结果骨化三醇可以在ALA之前作为无毒预处理方案施用，以显著增强ALA诱导的PpIX水平和荧光。与正常细胞相比，在胶质瘤中优先检测到PpIX水平的这种增加。此外，骨化三醇预处理的神经胶质瘤细胞表现出增加的细胞死亡后，ALA为基础的光动力疗法。此外，机制研究证明，卟啉合成酶粪卟啉原氧化酶的表达增加骨化三醇在mRNA水平。结论我们首次证明了一种简单、无毒和高效的预处理方案，以选择性地增强胶质瘤细胞中PpIX荧光和ALA-PDT的反应。这一发现表明，用骨化三醇加ALA联合治疗胶质瘤细胞可以提供有效和选择性的治疗方式，以增强ALA诱导的PpIX荧光质量，从而改善肿瘤组织的区分和PDT功效。
Abstract Background. Glioma recurrence frequently occurs close to the marginal area of the surgical cavity as a result of residual infiltrating glioma cells. Fluorescence-guided surgery with 5-aminolevulinic acid (ALA) for resection of gliomas has been used as an effective therapeutic approach to discriminate malignant tissue from brain tissue and to facilitate patient prognosis. ALA-based photodynamic therapy is an effective adjuvant treatment modality for gliomas. However, insufficient protoporphyrin IX (PpIX) accumulation may limit the applicability of fluorescence-guided resection and photodynamic therapy in the marginal areas of gliomas. Methods. To be able to understand how to overcome these issues, human glioma cells and normal astrocytes were used as the model system. Glioma cells and astrocytes were preconditioned with calcitriol for 48 hours and then incubated with ALA. Changes in ALA-induced PpIX fluorescence and cell survival after light exposure were assessed. Furthermore, expression of porphyrin synthetic enzymes in pretreated glioma cells was analyzed. Results. Calcitriol can be administered prior to ALA as a non-toxic preconditioning regimen to significantly enhance ALA-induced PpIX levels and fluorescence. This increase in PpIX level was detected preferentially in glioma versus normal cells. Also, calcitriol pretreated glioma cells exhibited increased cell death following ALA-based photodynamic therapy. Furthermore, mechanistic studies documented that expression of the porphyrin synthesis enzymes coproporphyrinogen oxidase was increased by calcitriol at the mRNA level. Conclusion. We demonstrated for the first time a simple, non-toxic and highly effective preconditioning regimen to selectively enhance PpIX fluorescence and the response of ALA-PDT in glioma cells. This finding suggests that the combined treatment of glioma cells with calcitriol plus ALA may provide an effective and selective therapeutic modality to enhance ALA-induced PpIX fluorescent quality for improving discrimination of tumor tissue and PDT efficacy.