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FOS 介导的自噬激活在基于吲哚菁绿的光动力疗法治疗黑色素瘤中的作用。

The role of FOS-mediated autophagy activation in the indocyanine green-based photodynamic therapy for treating melanoma.

机构信息

Department of Dermatology and Venereology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.

Department of Dermatology and Venereology, Hangzhou Third People's Hospital, Hangzhou, Zhejiang 310000, China.

出版信息

J Photochem Photobiol B. 2021 Jan;214:112101. doi: 10.1016/j.jphotobiol.2020.112101. Epub 2020 Dec 5.

DOI:10.1016/j.jphotobiol.2020.112101
PMID:33316624
Abstract

The morbidity and mortality of melanoma which accounts for 90% of cutaneous neoplasm-related deaths is growing over the last few decades. Common treatments for melanoma are limited to poor tissue selectivity, high toxicity and drug resistance. Photodynamic therapy (PDT) is an effective adjuvant therapy and could be a promising therapy for melanoma. Multiple mechanisms are involved in PDT and programmed cell death (PCD) which comprises of autophagy and apoptosis is likely to be a critical one. Whereas, the molecular mechanism and subsequent effect of PDT-induced autophagy in melanoma are still unclear. In this study, we first analyzed gene expression data in the TCGA and GEO databases to clarify that PDT-induced-autophagy improved the prognosis of melanoma. The expression of FOS which generally defined as an immediate-early gene (IEG) and related to cell autophagy was found significantly elevated after PDT. To further investigate whether FOS played a key role in PDT-induced-autophagy of melanoma, we first determined the optimum concentration of ICG solution for autophagy observation. Then, relative FOS expression was detected at mRNA and protein level and cell autophagy was observed by western blot and flow cytometry. We found that ICG-PDT treatment could significantly elevate FOS expression in SKCM B16 cells, and FOS promoted ICG-PDT-induced cell autophagy. To sum up, our data indicated that FOS was involved in ICG-PDT-induced-autophagy in melanoma and furthermore improved the prognosis of melanoma.

摘要

过去几十年间,黑色素瘤的发病率和死亡率(占皮肤肿瘤相关死亡人数的 90%)一直在上升。黑色素瘤的常见治疗方法仅限于组织选择性差、毒性高和耐药性等问题。光动力疗法(PDT)是一种有效的辅助疗法,可能是黑色素瘤有前途的治疗方法。PDT 涉及多种机制,其中程序性细胞死亡(PCD)包括自噬和细胞凋亡,可能是一个关键机制。然而,PDT 诱导的自噬在黑色素瘤中的分子机制和后续效应尚不清楚。在这项研究中,我们首先分析了 TCGA 和 GEO 数据库中的基因表达数据,以阐明 PDT 诱导的自噬改善了黑色素瘤的预后。在 PDT 后,通常被定义为即时早期基因(IEG)且与细胞自噬相关的 FOS 表达明显升高。为了进一步研究 FOS 是否在 PDT 诱导的黑色素瘤自噬中起关键作用,我们首先确定了用于自噬观察的最佳 ICG 溶液浓度。然后,通过 Western blot 和流式细胞术检测相对 FOS 表达在 mRNA 和蛋白水平上,并观察细胞自噬。我们发现 ICG-PDT 处理可显著上调 SKCM B16 细胞中的 FOS 表达,且 FOS 促进 ICG-PDT 诱导的细胞自噬。总之,我们的数据表明 FOS 参与了黑色素瘤中的 ICG-PDT 诱导的自噬,并且进一步改善了黑色素瘤的预后。

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