人食管癌荷瘤裸鼠光动力效应机制的初步研究  

Mechanism of photodynamic therapy against human esophageal carcinoma xenografts in nude mice

作　　者：陈晓华[1] 罗荣城[1] 李黎波[1] 丁雪梅[1] 吕成伟[1] 周小平[1] 严晓[1] 

机构地区：[1]南方医科大学南方医院肿瘤中心,广东广州510515

出　　处：《南方医科大学学报》2009年第11期2222-2224,共3页Journal of Southern Medical University

基　　金：中国临床肿瘤学科学基金(CSCO-康莱特基金)(Y-2005-0013)

摘　　要：目的探讨光动力治疗(photodynamic therapy,PDT)对人食管癌细胞Eca-109荷瘤裸鼠的作用机制。方法通过皮下接种Eca-109细胞建立人食管鳞癌荷瘤裸鼠模型,并将其随机分为血卟啉衍生物(Hematoporphyrin derivative,HpD)光动力治疗组(给予HpD及光照),单纯照光组(仅给予光照),单纯光敏剂组(仅给予HpD)及空白对照组。腹腔注射HpD24h后前两组行光照(光能量密度为120J/cm2),3d后处死所有裸鼠并检测瘤组织丙二醛(MDA)含量,免疫组化检测caspase-3并HE染色观察。结果HpD-PDT组与空白对照组,单纯照光组,单纯光敏剂组的MDA含量相比均显著增高(P<0.01),而后3组之间MDA含量均无明显差异(P>0.05)。HpD-PDT组与空白对照组间caspase-3蛋白阳性率无明显差异(P>0.05)。光镜下,HE染色仅HpD-PDT组可见大片均质红染的坏死物。结论HpD-PDT对人食管癌荷瘤裸鼠的作用机制主要是通过光照产生单态氧直接损伤肿瘤细胞并在过氧化反应中产生MDA,其凋亡途径中caspase-3可能未激活,即其凋亡途径可能是不依赖caspase-3通路的。Objective To investigate the mechanism of photodynamic therapy （PDT） in nude mice bearing human esophageal cancer cell line Eca-109 xenografts. Methods A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative （HpD）-PDT group （given HpD and laser irradiation）, exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 J/cm^2 delivered via a DIOMED 630 PDT system 24 h after intraperitoneat-HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde （MDA） production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue. Results The MDA level was signifieantly higher in HpD-PDT group than in the other 3 groups （P〈0.01）, and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group （P〉0.05）. Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining. Conclusion In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.

关 键 词：血卟啉衍生物 光动力疗法 丙二醛 免疫组化 

分 类 号：R735.1[医药卫生—肿瘤]