整合素靶向光动力学疗法对胰腺癌细胞的影响  

Effects of integrin-targeted photodynamic therapy on pancreatic carcinoma cell

作　　者：倪倩雯[1] 杨姗莹[1] 瞿春莹[1] 周敏[1] 赵鹏程[2] 张建成[2] 徐雷鸣[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化内镜诊治部上海市小儿消化与营养重点实验室,200092 [2]上海大学材料工程学院

出　　处：《中华消化杂志》2013年第4期253-258,共6页Chinese Journal of Digestion

基　　金：上海市卫生局重点项目（2010009）;上海市小儿消化与营养重点实验室资助项目（11DZ2260500）

摘　　要：目的探讨整合素靶向光动力学疗法（PDT）对人胰腺癌的体外抗癌作用。方法将胰腺癌SWl990细胞分成4组，以不加量子点、无光辐照培养的细胞作为空白对照，另设单纯光辐照组、光敏剂组、PDT组。合成量子点-精氨酸-甘氨酸-天冬氨酸（RGD）整合素探针，利用激光共聚焦显微镜验证其靶向性，将其作为光敏剂进行PDT。用荧光显微镜观察各组处理后48h胰腺癌细胞的形态学变化。MTT法、流式细胞术（FCM）法检测细胞增殖、凋亡和周期的变化。RT-PCR法检测各处理组细胞髓样细胞白血病-1（Mcl-1）、蛋白激酶B（Akt）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）表达。荧光探针检测各组活性氧表达。组间比较采用单因素方差分析，分析PDT组的治疗效果。结果量子点-RGD探针能有效靶向标记胰腺癌细胞。MTT法PDT组24、48、72h时的胰腺癌细胞增殖相对抑制率均高于空白对照组，差异有统计学意义（F=73．00、85．10、126．58，P均〈0．01）。FCM法结果示48h时PDT组细胞凋亡率（17．860％±1．230％）高于其他各组（F=130．617，P〈O．01）；细胞GO／G1期（69．14％±2．63％）和S期（24．41％±2．67％）出现阻滞（P均〈0．05）。PDT组增殖、凋亡相关基因Mcl-1、Akt的mRNA表达低于其他各组，而凋亡诱导配体TRAILmRNA表达高于其他各组（F=567．456、446．817，145．238，P均〈0．05）。PDT组活性氧水平高于其他各组（F=3262．559，P〈0．01）。结论量子点-RGD整合素靶向探针介导的PDT能明显抑制胰腺癌细胞增殖，促进细胞凋亡。Objective To investigate the anti-carcinoma role of integrin targeted photodynamic therapy （PDT） on pancreatic carcinoma cells in vitro. Methods Pancreatic carcinoma cells SW1990 were divided into four groups~ cells without quantum dots （QDs） and light-treated as blank control group, pure light-treated group, photosensitizer group and PDT group. The targeting of QDs- arginine, glycine, aspartic acid （RGD） and integrin probe was confirmed by laser confocal microscopy. And as a photosensitizer for photodynamic therapy, after treated for 48 hours the morphology changes of pancreatic carcinoma cells of each group were observed. After 48 hours, the cell proliferation, apoptosis and cell cycle changes were detected by methyl thiazolyl tetrazolium （MTT） assay and flowcytometry （FCM）. The expressions of myeloid cell leukemia-1 （Mc/-1）, protein kinase B（Akt） and tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） were detected by reverse transcriptase polymerase chain reaction（RT-PCR）. The amount of reactive oxygen species （ROS） of each group were evaluated by fluorescence probe. One-way ANOVA was performed for comparison between groups to analyze the treatment effects of PDT group. Results The QDs-RGD probe could effectively targeting pancreatic carcinoma cells. The MTT results indicated that the relative inhibition rate of pancreatic carcinoma cells proliferation of PDT group was statistically higher than that of the other groups at 24, 48, 72 h （F=73.00, 85.10, 126.58; all P〈0.01）. The FCM results revealed that the cell apoptosis rate of PDT group （17. 860%±1. 230%） was higher than that of the other groups （F= 130. 617, P〈0. 01） and cell cycle G0/G1 phase （69. 14%± 2. 63%） and S phase （24.41%± 2.67% ） retardance was also significant （all P〈0.05）. The expression of proliferation and apoptosis related gene Mcl-1 and Akt at mRNA level was lower than that of the other groups however the expression of apoptosis-inducing ligand TRAIL at mRNA

关 键 词：胰腺肿瘤 整合素类 分子探针 光化学疗法 细胞凋亡 

分 类 号：R735[医药卫生—肿瘤]