简介：AIM:Toinvestigatethebiologicaleffectsofinternalirradiation,andthetherapeuticeffectivenesswasassessedof131I-labeledanti-epidermalgrowthfactorreceptor（EGFR）liposomes,derivedfromcetuximab,whenusedasatumor-targetingcarrierinacolorectalcancermousemodel.METHODS:WedescribedtheliposomesandcharacterizedtheirEGFR-targetedbindingandcellularuptakeinEGFR-overexpressingLS180colorectalcancercells.Afterintra-tumorinjectionsof74MBq（740MBq/mL）131I-antiEGFR-BSA-PCL,weinvestigatedthebiologicaleffectsofinternalirradiationandthetherapeuticefficacyof131I-antiEGFR-BSA-PCLoncolorectalcancerinamaleBALB/cmousemodel.Tumorsize,bodyweight,histopathology,andSPECTimagingweremonitoredfor33dpost-therapy.RESULTS:Therapidradioiodineuptakeof131I-antiEGFR-BSA-PCLand131I-BSA-PCLreachedmaximumlevelsat4hafterincubation,andthe131Iuptakeof131I-antiEGFR-BSA-PCLwashigherthanthatof131I-BSAPCLinvitro.The131Itissuedistributionassayrevealedthat131I-antiEGFR-BSA-PCLwasmarkedlytakenupbythetumor.Furthermore,atissuedistributionassayrevealedthat131I-antiEGFR-BSA-PCLwasmarkedlytakenupbythetumorandreacheditsmaximaluptakevalueof21.0±1.01%ID/g（%ID/gisthepercentageinjecteddosepergramoftissue）at72hfollowingtherapy;thedrugconcentrationinthetumorwashigherthanthatintheliver,heart,colon,orspleen.Tumorsizemeasurementsshowedthattumordevelopmentwassignificantlyinhibitedbytreatmentswith131I-antiEGFR-BSA-PCLand131I-BSA-PCL.Thevolumeoftumorincreased,andtreatmentratewith131I-antiEGFR-BSA-PCLwas124%±7%,lowerthanthatwith131I-BSA-PCL（127%±9%）,131I（143%±7%）,andnormalsaline（146%±10%）.Thepercentagelossesinoriginalbodyweightswere39%±3%,41%±4%,49%±5%,and55%±13%,respectively.Thebestsurvivalandcurerateswereobtainedinthegrouptreatedwith131I-antiEGFR-BSA-PCL.Theanimalsinjec

简介：目的探讨CCAAT/增强子结合蛋白α（C/EBPα）在肝癌细胞增殖中的作用及其机制.方法利用靶向C/EBPα的RNAi慢病毒感染Hep3B肝癌细胞系,构建C/EBPα肝癌细胞系敲减模型.采用qRT-PCR和Westernblot分别检测C/EBPαmRNA和蛋白表达水平,采用CCK-8检测敲减C/EBPα后对Hep3B细胞增殖的影响,采用在正常高葡萄糖（NG,4.5g/L）和低葡萄糖（LG,1g/L）条件下培养细胞的增殖变化,采用Westernblot法检测不同葡萄糖浓度条件下在C/EBPα敲减细胞和对照细胞乙酰葡糖胺转移酶（OGT）、乙酰葡糖胺水解酶（OGA）和整个O-GlcNAc糖基化水平.结果靶向C/EBPα的RNAi慢病毒感染Hep3B肝癌细胞后,C/EBPαmRNA水平下调了（7.5±2.3）倍（P〈0.05）,蛋白表达水平下调了（8.8±0.25）倍（P〈0.001）,提示C/EBPα敲减细胞系构建成功;敲减C/EBPα后明显促进肝癌细胞的体外增殖;在低葡萄糖条件下刺激48h和72h,敲减C/EBPα分别促进细胞增殖15.4%（P〈0.05）和25.0%（P〈0.01）;敲减C/EBPα后细胞OGA蛋白表达水平在正常高糖和低糖刺激24h和48h时分别下调了70.1%（P〈0.01）、51.4%（P〈0.05）和61.2%（P〈0.05）,整体O-GlcNAc糖基化表达水平上调,在低糖刺激48h时升高80.6%.结论敲减转录因子C/EBPα可以提高细胞整体O-GlcNAc糖基化水平,从而促进肝癌细胞的体外增殖.