纳米靶向联合激光增强褪黑素的抗胃癌效应与NK细胞免疫调节作用  

Nanoparticle targeting combined with laser enhances melatonin’s anti-gastric cancer effects and its immunomodulatory role on NK cells

作　　者：林晋[1,3] 王秀蓉 林宸伊 刘卉 Lin Jin;Wang Xiurong;Lin Chenyi;Liu Hui(School of Medicine,Fujian Health College,Fuzhou 350101,China;School of Basic Medicine,Fujian Medical University,Fuzhou 350122,China;Key Laboratory of Stem Cell Engineering and Regenerative Medicine,Fujian Province University,Fuzhou 350122,China)

机构地区：[1]福建卫生职业技术学院医学院,福州350101 [2]福建医科大学基础医学院,福州350122 [3]干细胞工程与再生医学福建省高校重点实验室,福州350122

出　　处：《中国组织化学与细胞化学杂志》2024年第4期338-346,共9页Chinese Journal of Histochemistry and Cytochemistry

基　　金：福建省中青年教师教育科研项目(JAT210790);福建省自然科学基金面上项目(2021J01674)。

摘　　要：目的研究纳米材料硫化亚铁荷载褪黑素(FeS@MLT)对胃癌的影响及其对NK细胞穿孔素和颗粒酶B表达的调控。方法用不同浓度硫化亚铁、褪黑素、FeS@MLT分别干预胃癌细胞,CCK-8法检测细胞增殖率,PI染色法测细胞凋亡。裸鼠皮下荷胃癌成功后用褪黑素、FeS@MLT、褪黑素+激光、FeS@MLT+激光分别干预后,测肿瘤体积、局部温度、血常规,HE染色观察重要脏器及肿瘤组织形态,免疫印迹法检测肿瘤组织穿孔素、颗粒酶B蛋白的表达。结果体外实验发现褪黑素组细胞凋亡率高于FeS@MLT组;体内实验各处理组血常规及脏器形态未见明显异常,FeS@MLT+激光组较褪黑素组肿瘤局部温度增高,肿瘤组织体积减小、坏死明显,穿孔素及颗粒酶B蛋白表达升高。结论FeS@MLT有生物安全性,其联合激光干预效果优于单纯褪黑素干预。升高肿瘤局部温度、增加穿孔素和颗粒酶B蛋白表达,是其抗肿瘤可能机制之一。Objective To investigate the effects of iron disulfide nanoparticles loaded with melatonin(FeS@MLT)on gastric cancer and its regulation of perforin and granzyme B expression in NK cells.Methods Gastric cancer cells were treated with different concentrations of iron disulfide,melatonin,and [e-mail] proliferation was assessed using the CCK-8 assay,and apoptosis was measured by PI staining.After successfully establishing subcutaneous gastric cancer in nude mice,the animals were treated with melatonin,FeS@MLT,melatonin+laser,or FeS@MLT+laser.Tumor volume,local temperature,and blood routine were measured,and HE staining was used to observe the morphology of major organs and tumor tissue.Western blotting was used to detect the expression of perforin and granzyme B proteins in tumor tissue.Results In vitro experiments showed that the apoptosis rate in the melatonin group was higher than that in the FeS@MLT group.In vivo,there were no significant abnormalities in blood routine and organ morphology across the treatment groups.The FeS@MLT+laser group showed a higher local tumor temperature than the melatonin group,with a reduction in tumor volume,significant necrosis,and an increase in the expression of perforin and granzyme B proteins.Conclusion FeS@MLT is biologically safe,and its combined laser intervention is more effective than melatonin treatment alone.Increasing local tumor temperature and enhancing the expression of perforin and granzyme B proteins may be one of its mechanisms for anti-tumor activity.

关 键 词：褪黑素 硫化亚铁 穿孔素 颗粒酶B 胃癌 激光 联合治疗 

分 类 号：R365[医药卫生—病理学]