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首页> 外文期刊>Photodiagnosis and Photodynamic Therapy >Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress-activated p38 MAPK and JNK signal pathway in H460 cell lines
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Photodynamic therapy (PDT) - Initiation of apoptosis via activation of stress-activated p38 MAPK and JNK signal pathway in H460 cell lines

机译：光动力疗法（PDT）-通过激活H460细胞系中的应激激活的p38 MAPK和JNK信号通路来启动凋亡

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Aims: The purpose of this study was to investigate the photoefflcacies of protoporphyrin IX(PplX) generated by drug precursor 5-aminolevulinic acid (ALA) and its hexyl ester (H-ALA) ontwo human non-small lung carcinoma cell lines (H460/Bcl-2 and H460eo).Main methods: Drug uptake and the photoefficacies of PplX were measured by flow cytometryand MTT assay; while the mode of cell death and alternation of signal transduction pathwayswere studied with 4',6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis,respectively.Key findings: The flow cytometric analysis of H-ALA (5 μM) uptake revealed optimal fluorescentintensity at 8h incubation, while ALA (0.5 mM) was still far from saturation. The LD_(30) of H-ALA-PDTwas 30μM, 2J/cm2, whilethe LD_(30) of ALA-PDT was 3mM, 2J/cm2. The dark toxidtiesmediated by both pro-drug H-ALA and ALA were negligible. By DAPl staining, apoptotic cell deathwas observed. In addition, by Western blot analysis, H-ALA- and ALA-mediated PDT initiatedapoptotic cell death via the up-regulation and activation of p38 mitogen activated proteinkinase (MAPK), the stress-activated c-jun N-terminal kinases (JNK) and ERK.Sisnipcance: These results suggested that H-ALA and ALA mediated PDT displayed similar photo-cytotoxicities towards the two non-small lung cancer cells. Our present study also demonstratesH-ALA or ALA mediated PDT in H460 cells are closely related to the activation of p38 MAPK andJNK signalling pathway.
机译：目的：本研究旨在研究药物前体5-氨基乙酰丙酸（ALA）及其己酸酯（H-ALA）产生的原卟啉IX（PplX）对两种人非小细胞肺癌细胞（H460 / Bcl-2和H460 / neo）。主要方法：流式细胞术和MTT法检测PplX的药物吸收和光效率。通过4'，6-二6-基-2-苯基吲哚（DAPI）染色和Western blot分析分别研究了细胞死亡的模式和信号转导途径的改变。主要发现：H-ALA（5μM）的流式细胞仪分析吸收显示在8h的孵育中最佳荧光强度，而ALA（0.5 mM）仍未达到饱和。 H-ALA-PDT的LD_（30）为30μM，2J / cm2，而ALA-PDT的LD_（30）为3mM，2J / cm2。由前药H-ALA和ALA介导的深色氧化微不足道。通过DAP1染色，观察到凋亡细胞死亡。此外，通过蛋白质印迹分析，H-ALA和ALA介导的PDT通过上调和激活p38丝裂原活化蛋白激酶（MAPK）（应力激活的c-jun N末端激酶（JNK））来引发细胞凋亡。和ERK.Sisnipcance：这些结果表明，H-ALA和ALA介导的PDT对两种非小肺癌细胞显示出相似的光细胞毒性。我们的研究还证明，H460细胞中H-ALA或ALA介导的PDT与p38 MAPK和JNK信号通路的激活密切相关。

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