PTEN and TRAIL genes loaded zein nanoparticles as potential therapy for hepatocellular carcinoma
PTEN and TRAIL genes loaded zein nanoparticles as potential therapy for hepatocellular carcinoma
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DOI：
10.1080/1061186x.2017.1289536
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发表时间：
2017-07-01
影响因子：
4.5
通讯作者：
Rashed, Laila Ahmed
中科院分区：
文献类型：
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作者：
El Sharkawi, Fathia Zaki;Ewais, Shaimaa Mohammed;Rashed, Laila Ahmed
基因治疗是近年来治疗肝细胞癌的新方法之一。迫切需要开发一种载体或载体，能够选择性地、有效地将基因以最小的毒性传递到靶细胞。在本研究中，将磷酸酶和紧张素同源物（PTEN）和肿瘤坏死因子（TNF）相关的凋亡诱导配体（TRAIL）基因装载到玉米蛋白纳米颗粒（ZNPs）上。以肝肿瘤细胞（HepG2）和hcc诱导大鼠为动物模型，对配制的PTEN和trail负载的ZNPs进行体外和体内潜在的抗肿瘤作用检测。p53、VGEF和MMP-2的mRNA表达作为动物肝组织凋亡、血管生成和转移的标志物。结果表明，PTEN和trail负载的ZNPs对HepG2细胞株均具有抗增殖活性，IC50值分别为0.09、0.25 μ g/ml。体内实验证实，治疗动物肝脏组织中VEGF和MMP- 2 mRNA表达降低，P53表达水平升高。因此，作者介绍了基因治疗和纳米技术之间的新整合，以PTEN和trail负载的ZNPs的形式，被证明有潜力用于HCC的基因治疗。
Gene therapy is one of the recent approaches in treatment of hepatocellular carcinoma (HCC). Development of a vector or vehicle that can selectively and efficiently deliver the gene to target cells with minimal toxicity is an urgent demand. In the present study, phosphatase and tensin homolog (PTEN) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) genes were loaded to zein nanoparticles (ZNPs). The formulated PTEN and TRAIL-loaded ZNPs were tested for their in vitro and in vivo potential antitumor efficacy using liver tumor cells (HepG2) and HCC-induced rats as animal model. Also, mRNA expression of p53, VGEF and MMP-2 were carried out as markers of apoptosis, angiogenesis and metastasis in animal liver tissues. The results of the study showed that both PTEN and TRAIL-loaded ZNPs proved anti-proliferative activity against HepG2 cell lines with IC50 values of 0.09, 0.25 mu g/ml, respectively. In vivo assay confirmed decrease in mRNA expression of both VEGF and MMP- 2 with increased in P53 expression level in liver tissues of the treated animals. Therefore, authors introduced new integration between gene therapy and nanotechnology in the form of PTEN and TRAIL-loaded ZNPs that proved potential to be used in gene therapy for the treatment of HCC.