Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene.
Efficient inhibition of ovarian cancer by degradable nanoparticle-delivered survivin T34A gene.
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可降解纳米颗粒递送的生存素 T34A 基因有效抑制卵巢癌
DOI：
10.2147/ijn.s93496
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发表时间：
2016
影响因子：
8
通讯作者：
Gou M
中科院分区：
文献类型：
--
作者：
Luo L;Du T;Zhang J;Zhao W;Cheng H;Yang Y;Wu Y;Wang C;Men K;Gou M
基因治疗在卵巢癌的治疗中具有广阔的应用前景。阻断生存素蛋白的功能可导致癌细胞的生长抑制。在此，我们使用可降解的肝素-聚乙烯亚胺（HPEI）纳米颗粒来递送显性阴性的人生存素T34 A（hs-T34 A）基因来治疗卵巢癌。表征HPEI纳米颗粒，发现其动态直径为66±4.5 nm，ζ电位为27.1±1.87 mV。构建的hs-T34 A基因表达质粒可通过HPEI纳米粒有效转染卵巢癌SKOV 3细胞，且细胞毒性较低。腹腔注射HPEI/hs-T34 A复合物可显著抑制SKOV 3人卵巢癌小鼠异种移植模型中的肿瘤生长。此外，根据我们的结果，在体外和体内都观察到明显的癌细胞凋亡。综上所述，所制备的HPEI/hs-T34 A制剂显示出在卵巢癌基因治疗中的潜在应用。
Gene therapy has promising applications in ovarian cancer therapy. Blocking the function of the survivin protein could lead to the growth inhibition of cancer cells. Herein, we used degradable heparin–polyethyleneimine (HPEI) nanoparticles to deliver a dominant-negative human survivin T34A (hs-T34A) gene to treat ovarian cancer. HPEI nanoparticles were characterized and were found to have a dynamic diameter of 66±4.5 nm and a zeta potential of 27.1±1.87 mV. The constructed hs-T34A gene expression plasmid could be effectively delivered into SKOV3 ovarian carcinoma cells by HPEI nanoparticles with low cytotoxicity. Intraperitoneal administration of HPEI/hs-T34A complexes could markedly inhibit tumor growth in a mouse xenograft model of SKOV3 human ovarian cancer. Moreover, according to our results, apparent apoptosis of cancer cells was observed both in vitro and in vivo. Taken together, the prepared HPEI/hs-T34A formulation showed potential applications in ovarian cancer gene therapy.