Attenuation of photodynamically induced apoptosis by an RGD containing peptide
Attenuation of photodynamically induced apoptosis by an RGD containing peptide
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DOI：
10.1039/b109979e
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发表时间：
2002-04-01
影响因子：
3.1
通讯作者：
Weber, JM
中科院分区：
文献类型：
--
作者：
Allen, CM;Sharman, WM;Weber, JM
研究工作集中在改进已经建立的光动力疗法（PDT）方案上。使用辅助治疗就是这样一种途径。整联蛋白类受体介导细胞外基质信号通过错综复杂的细胞通路的复杂迷宫。已知Arg-Gly-Asp（RGD）基序与25种已知的整联蛋白受体类型中的几种结合。在大多数情况下，可溶性RGD肽在许多细胞系中诱导凋亡。在这项研究中。研究了含RGD的肽对二磺基邻苯二甲酸铝（AlPcS 2adj）的光动力作用的影响。在可溶性R ⑶存在下用AIPcS（2adj）处理腺癌肺癌细胞（A549）和鼠乳腺癌细胞（EMT-6）。在升高的RGD浓度（10 mM）下，单独的肽诱导细胞凋亡。结果表明，在较低的浓度下，RGD废除PDT在两种细胞系中的凋亡作用，如通过MTT细胞毒性试验，核小体DNA梯状和凋亡小体的形成所评估的。在A549受体阳性细胞系中，当在LD 90条件下使用100 μ M的RGD肽时，RGD对细胞凋亡的保护作用更明显，该细胞系显示出超过70%的细胞存活率。研究了不同的参数以清楚地确定细胞杀伤的减弱不仅仅是由于肽对激发物质的淬灭。事实上，这种现象不是生物物理学的，而是生物学的。
Research efforts have focused on the improvement of already established photodynamic therapy (PDT) protocols. The use of adjunct therapies is one such route. The integrin class of receptors mediates extracellular matrix signals through a complex maze of intertwining cellular pathways. The Arg-Gly-Asp (RGD) motif is known to bind to several of the 25 known integrin receptor types. Soluble RGD peptides under most circumstances induce apoptosis in a number of cell lines. In this study.. the effect of an RGD-containing peptide on the photodynamic action of aluminium disulfophthalocyanine (AlPcS2adj) was investigated. Adenocarcinoma lung cancer cells (A549) and murine mammary cancer cells (EMT-6) were treated with AIPcS(2adj) in the presence of soluble RGD. At elevated RGD concentrations (10 mM) apoptosis was induced by the peptide alone. It was shown that at lower concentrations, RGD abrogated the apoptotic effect of PDT in both cell lines, as assessed by an MTT cytotoxicity assay, nucleosomal DNA laddering and the formation of apoptotic bodies. RGD protection against apoptosis was more pronounced in the A549 receptor positive cell line which exhibits over 70% cell survival when using 100 muM RGD peptide under LD90 conditions. Different parameters were investigated to clearly establish that the attenuation of cell killing was not solely due to quenching of the excited species by the peptide. Indeed, the phenomenon is not photophysical but biological.