Mamoon Abdel-Megid, Gamal-Eldeen Amira M, Ruppel Meghan E, Smith Randy J, Tsang Thomas, Miller Lisa M
Egyptian Atomic Energy Authority, Nasr City, Cairo, Egypt.
Photodiagnosis Photodyn Ther. 2009 Jun;6(2):105-16. doi: 10.1016/j.pdpdt.2009.05.002.
Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.
Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers.
In the cell death pathway, (1)O(2) generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15 min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-kappaB P65, and the enhancement of DNA fragmentation, and histone acetylation.
ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.
光动力疗法(PDT)是一种有前景的浅表癌治疗方法。然而,由于黑色素含量高,黑色素瘤的治疗效果不佳。吲哚菁绿(ICG)具有近红外吸收(700 - 800 nm),而黑色素在该区域吸收不强。本研究探讨ICG作为人黑色素瘤光动力治疗剂的效率及其在细胞死亡途径中的作用机制。
将人皮肤黑色素瘤细胞(Sk - Mel - 28)与ICG孵育,然后暴露于低功率钛宝石激光下。使用同步加速器辅助傅里叶变换红外显微光谱和层次聚类分析来评估细胞损伤以及脂质、蛋白质和核酸的变化。通过分析细胞活力以及凋亡和坏死标志物来确定细胞死亡途径。
在细胞死亡途径中,激光照射仅15分钟后,单线态氧(¹O₂)的产生引发了一系列快速的后果,触发细胞凋亡,包括细胞色素c的释放、总半胱天冬酶、半胱天冬酶 - 3和半胱天冬酶 - 9的激活、核因子κB P65的抑制以及DNA片段化和组蛋白乙酰化的增强。
ICG/PDT可有效且快速地诱导人黑色素瘤细胞凋亡,可被视为一种治疗黑色素瘤局部治疗的新方法。