Melatonin displays antitumor activity in several types of malignancies; however, the best delivery route and the underlying mechanisms are still unclear. Alternative non-invasive delivery route based on transdermal administration of melatonin by cryopass-laser treatment demonstrated efficiency in reducing the progression of LNCaP prostate tumor cells xenografted into nude mice by impairing the biochemical pathways affecting redox balance. Here, we investigated the impact of transdermal melatonin on the tumor dimension, microenvironment structure, and SIRT1-modulated pathways. Two groups (vehicle cryopass-laser and melatonin cryopass-laser) were treated for 6 weeks (3 treatments per week), and the tumors collected were analyzed for hematoxylin eosin staining, sirius red, and SIRT1 modulated proteins such as PGC-1α, PPARγ, and NFkB. Melatonin in addition to simple laser treatment was able to boost the antitumor cancer activity impairing the tumor microenvironment, increasing the collagen structure around the tumor, and modulating the altered SIRT1 pathways. Transdermal application is effective, safe, and feasible in humans as well, and the significance of these findings necessitates further studies on the antitumor mechanisms exerted by melatonin.
褪黑素在多种恶性肿瘤中显示出抗肿瘤活性,但其最佳给药途径及潜在机制尚不明确。基于冷冻透皮激光技术的新型非侵入性给药途径,通过干扰影响氧化还原平衡的生化通路,有效抑制了裸鼠体内LNCaP前列腺肿瘤细胞移植瘤的进展。本研究探讨了透皮褪黑素对肿瘤体积、微环境结构及SIRT1调控通路的影响。将实验对象分为两组(冷冻激光对照组与褪黑素冷冻激光组),进行为期6周(每周3次)的治疗,并对收集的肿瘤组织进行苏木精-伊红染色、天狼星红染色及SIRT1调控蛋白(PGC-1α、PPARγ、NFkB)检测。结果显示,相较于单纯激光治疗,联合褪黑素能增强抗肿瘤活性,其机制包括破坏肿瘤微环境、增加肿瘤周围胶原结构、调节异常的SIRT1信号通路。透皮给药在人体应用中同样具有高效性、安全性与可行性,这些发现的重要意义提示有必要对褪黑素的抗肿瘤机制开展进一步研究。