DOX联合HMME-PDT对人肝癌细胞HepG2联合作用的研究  

The Initial Research of the Effect of DOX Combined with HMME-PDT on Human Hepatoma Cells HepG2

作　　者：刘佳[1] 李晓原[1] 刘建中[2] 段艳芳[2] 吕琳[1] 李燕[3] 

机构地区：[1]中山大学中山医学院生物医学工程系,广东广州510080 [2]中山大学中山医学院生物学教研室,广东广州510080 [3]中山大学医学教学实验中心,广东广州510080

出　　处：《中国医学物理学杂志》2008年第5期819-822,共4页Chinese Journal of Medical Physics

摘　　要：目的:初步探讨阿霉素(DOX)联合血卟啉单甲醚介导的光动力疗法(HMME-PDT)对人肝癌细胞(HepG2)的作用及可能的机制。方法:实验分对照组、单独PDT组、单独DOX组和联合作用组。PDT组所用的光敏剂剂量为2.5μg/mL,能量密度为0.2 J/cm2、0.4 J/cm2、0.8 J/cm2、1.6 J/cm2和3.2 J/cm2。DOX组所用的DOX浓度为0.1μg/mL、0.2μg/mL和0.4μg/mL。联合作用为不同剂量单独作用的组合,联合时序为PDT后立即加入阿霉素(PDT+DOX)或阿霉素先于PDT24 h加入(DOX+PDT)。MTT法检测24 h后的细胞活性抑制率,并用金氏公式分析联合效应。荧光显微镜观察不同处理组阿霉素的摄取情况。结果:MTT法结果表明,联合作用的细胞抑制率高于单独作用,这在PDT+DOX的联合时序作用中表现更为明显。金氏公式分析表明,PDT+DOX的联合作用相对DOX+PDT的联合作用产生更明显的协同或相加效应。荧光显微镜实验可以观察到联合作用明显提高了细胞对阿霉素的摄取,并且随着联合剂量的加大摄取加强。结论:相对单独作用,联合作用有更高的细胞活性抑制率,联合效应与联合时序有关,PDT+DOX的联合作用的联合效果好。联合作用产生相加或协同效应的机制之一可能是因为PDT处理改变了细胞膜通透性从而更有利于细胞对阿霉素的摄取,最终提高作用效果。Objective： To evaluate the synergistic or additive effect of Dox combined with HMME-PDT to HepG2 cells, and to probe the might mechanism of this effect. Methods： Cells were divided into different groups and treated with PDT, DOX, PDT＋DOX and DOX＋PDT. In PDT procedure, the concentration of HMME was 2.5ug/mL, and the energy densities were 0.2 J/cm^2-3.2 J/cm^2. The doses of DOX used were 0.1 ug/mL-0.4 ug/mL. The combined treatments were the combination of different monotherapy doses. We added the DOX either after PDT （PDT＋DOX） or before PDT （DOX＋PDT）.The cell vital inhibition was analyzed by MTT assay. The Jin＇s formula was used to analyze their synergic inhibitory effect. Fluorescence microscopy was used to observe the uptake of DOX. Results： The cell vital inhibition after combined treatment was significantly enhanced compared to monotherapy detected by MTT assay; especially in PDT＋DOX combined treatment. The Jin＇s formula indicated that combined treatment have the synergistic or additive effect. Using fluorescence microscopy we can observe the higher uptake of DOX in combined group than PDT or DOX alone group. Conclusions： DOX combined with HMME-PDTcan enhance the cell vital inhibition of HepG2 compared to monotherapy. Different combined treatments had different effects. One of the mechanisms of the synergistic or additive effect, might be associated with that pre-treatment by PDT had increased the cellular membrane permeability followed by increased DOX uptake.

关 键 词：血卟啉单甲醚 光动力 阿霉素 协同作用 HEPG2细胞 

分 类 号：R774[医药卫生—眼科]