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聚酰胺-胺树枝状大分子脂质体介导的生存素反义寡核苷酸通过诱导凋亡抑制肝癌细胞增殖。

Polyamidoamine dendrimer liposome-mediated survivin antisense oligonucleotide inhibits hepatic cancer cell proliferation by inducing apoptosis.

作者信息

Han Shuai, Cai Zhai, Peng Liang, Li Zhou, Zhou Hua-Bin, Li Xiu-Qin, Fang Su-Zhen, Huang Zong-Hai, Cui Da-Xiang

机构信息

Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.

出版信息

Tumour Biol. 2014 May;35(5):5013-9. doi: 10.1007/s13277-014-1661-2. Epub 2014 Feb 3.

Abstract

Polyamidoamine dendrimer (PAMAM) is a new nanometer material, which can transfer the target genes to cells with high efficiency and lower toxicity. This study aims to evaluate antitumor effects of survivin antisense oligonucleotide (survivin-asODN) (carried by polyamidoamine dendrimer liposome) on hepatic cancer in nude mice. Hepatic cancer model was established by injecting SMMC-7721 cells subcutaneously into flanks of nude mice. Polyamidoamine dendrimer and liposome were mixed with survivin-asODN, respectively. The shape and size of complex were observed by transmission electron microscope, and zeta potential was measured by an analytical tool. Encapsulation efficiency and DNA loading level were determined by an ultraviolet spectrophotometer in centrifuging method. Expression of survivin in transplant tumor was measured by Western blotting. No significant difference appeared for diameter and envelopment ratio between PAMAM liposome-survivin-asODN and PAMAM-survivin-asODN (P > 0.05). Both zeta potential and transfection efficiency in PAMAM liposome-survivin-asODN were higher than that in PAMAM-survivin-asODN complex (P < 0.05). Expression of survivin protein and weight of tumors in transplanted tumors in PAMAM liposome-survivin-asODN group was less than that in PAMAM-survivin-asODN group (P < 0.05). Cell apoptosis rate in PAMAM liposome-survivin-asODN group was higher than that of PAMAM-survivin-asODN group (P < 0.05). In conclusion, polyamidoamine dendrimer liposome can deliver survivin-asODN into hepatic transplanted tumor cells effectively. Ployamidoamine dendrimer liposome-mediated survivin-asODN can inhibit hepatic cell proliferation by inducing apoptosis.

摘要

聚酰胺-胺树枝状大分子(PAMAM)是一种新型纳米材料,它能够将目标基因高效、低毒地转运至细胞。本研究旨在评估聚酰胺-胺树枝状大分子脂质体携带的生存素反义寡核苷酸(survivin-asODN)对裸鼠肝癌的抗肿瘤作用。通过将SMMC-7721细胞皮下注射到裸鼠侧腹建立肝癌模型。聚酰胺-胺树枝状大分子和脂质体分别与survivin-asODN混合。通过透射电子显微镜观察复合物的形态和大小,并用分析工具测量zeta电位。采用离心法通过紫外分光光度计测定包封率和DNA负载量。通过蛋白质免疫印迹法检测移植瘤中生存素的表达。PAMAM脂质体-survivin-asODN与PAMAM-survivin-asODN之间的直径和包封率无显著差异(P>0.05)。PAMAM脂质体-survivin-asODN的zeta电位和转染效率均高于PAMAM-survivin-asODN复合物(P<0.05)。PAMAM脂质体-survivin-asODN组移植瘤中生存素蛋白表达和肿瘤重量均低于PAMAM-survivin-asODN组(P<0.05)。PAMAM脂质体-survivin-asODN组的细胞凋亡率高于PAMAM-survivin-asODN组(P<0.05)。综上所述,聚酰胺-胺树枝状大分子脂质体能够有效地将survivin-asODN递送至肝移植瘤细胞。聚酰胺-胺树枝状大分子脂质体介导的survivin-asODN可通过诱导凋亡抑制肝细胞增殖。

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