Laboratory of Integrative Biology, Centro de Excelencia en Medicina Traslacional-Scientific and Technological Bioresource Nucleus (CEMT-BIOREN), Universidad de La Frontera, Temuco 4810296, Chile.
Department of Basic Sciences, School of Medicine, Universidad de La Frontera, Temuco 4811230, Chile.
Int J Mol Sci. 2020 May 8;21(9):3327. doi: 10.3390/ijms21093327.
Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of , and an upregulation of and genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions.
光动力疗法(PDT)已被用于治疗某些类型的非黑素瘤皮肤癌,并取得了良好的效果。然而,一些皮肤病变并未对这种治疗完全反应,表明存在潜在的 PDT 耐药表型。因此,必须确定新的治疗替代方案,以改善耐药性皮肤癌的 PDT。在这项研究中,我们分析了 PDT 耐药性 HSC-1 细胞的细胞活力、细胞内原卟啉 IX(PpIX)含量和亚细胞定位、增殖情况、细胞死亡、活性氧(ROS)检测和相对基因表达。PDT 耐药性 HSC-1 细胞显示出低数量的原卟啉 IX 和低水平的 ROS,因此细胞死亡率低。此外,耐药表型显示出下调 ,上调 和 基因。另一方面,表没食子儿茶素没食子酸酯(EGCG)增强了 MAL-PDT 的效果,增加了原卟啉 IX 和 ROS 的水平,并杀死了 100%的耐药细胞。皮肤鳞状癌细胞(HSC-1)的耐药性 MAL-PDT 模型是一种可靠且有用的工具,可以了解 PDT 的细胞毒性和细胞反应。这些耐药细胞已成功用表没食子儿茶素没食子酸酯(EGCG)敏化。体外表没食子儿茶素没食子酸酯(EGCG)作为增强剂在耐药细胞中 MAL-PDT 的效果有望用于治疗难治性皮肤癌病变。