纳米脂质体介导的结肠癌FL/TRAIL双基因治疗的体外体内评估

2012-04-04 08:15 来源:丁香园 作者:山东大学齐鲁医院普外科
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Cancer Lett 2012 Feb;315 (1): 69-77. [IF:4.864]  
Nanoliposome-mediated FL/TRAIL double-gene therapy for colon cancer: In vitro and in vivo evaluation.
Sun NF , Meng QY , Tian AL , Hu SY , Wang RH , Liu ZX , Xu L .
Department of the Surgery, Affiliated Jinan Central Hospital of Shandong University, Jinan 250013, China; Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
山东大学附属济南市中心医院,山东大学齐鲁医院普外科

Abstract
To investigate the therapeutic effects of cationic nanoliposome-mediated gene therapy combined with immunotherapy for colon cancer treatment. Recombinant plasmids containing green and red fluorescent protein reporter genes were constructed using gene cloning methods. Gene-carrying cationic nanoliposomes were prepared based on the electrostatic adherence principle and then transfected into dendritic cells (DC), which were transplanted into colon cancer cells. Recombinant plasmids containing green or red fluorescent protein reporter genes were successfully constructed by gene cloning and confirmed by restriction enzyme digestion and sequencing. Gene-carrying cationic nanoliposomes were transfected into colon cancer cells, and good gene expression was detected. A better level of apoptosis was observed in the combined group of tyrosine kinase receptor 3 ligand (FL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), while the lowest level was detected in the control group. The parameters in the FL and TRAIL groups were between the above-mentioned combined group. Cationic nanoliposomes have the advantage of being gene carriers. The joint therapeutic effects of the two genes are superior to those of a single gene. Gene therapy combined with immunotherapy has significant implications for cancer treatment.

摘要:
为了检测阳离子纳米脂质体介导的基因治疗联合免疫治疗结肠癌的治疗效果,我们利用基因克隆的方法构建含绿色和红色荧光蛋白的基因,然后基于静电粘附原则设计出携带阳离子纳米脂质体,然后转染树突状细胞(DC),然后被移植于结肠癌肿瘤细胞。通过基因克隆和限制性内切酶鉴定和测序,成功构建含绿色或红色荧光蛋白基因的重组质粒。携带基因阳离子纳米脂质体被转染进结肠癌细胞,检测到基因成功表达。联合检测酪氨酸激酶受体3配体(FL)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)组有一个更好水平的细胞凋亡,在对照组检测到凋亡水平最低。在FL和TRAIL组参数是在上述组之间。阳离子纳米脂质体具有携带基因的优势,两种基因的联合治疗效果优于单个基因。将基因治疗和免疫治疗结合治疗癌症会产生重大效果。

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