聚酰胺-胺型树枝状高聚合物介导Survivin反义寡核苷酸抑制人肝癌裸鼠 移植瘤生长的作用*☆

背景：采用反义寡核苷酸等治疗方法可以抑制凋亡抑制因子Survivin 的表达，从而诱导肿瘤细胞凋亡。目前使用Survivin治疗恶性肿瘤仍存在基因载体转染效率低下、不能长期稳定表达、易被酶降解等难题。 目的：观察聚酰胺-胺型树枝状高聚合物(polyamidoamine，PAMAM)脂质体介导Survivin-反义寡核苷酸对人肝癌裸鼠移植瘤的抑制作用。 方法：以人肝癌细胞SMMC-7721裸鼠皮下注射建立人肝癌裸鼠皮下移植瘤模型，将PAMAM脂质体和PAMAM分别与Survivin-反义寡核苷酸混合得到载反义基因转染复合物。测定复合物的zeta电位及包封率。将两种载基因复合物注射道裸鼠移植瘤体内，观察两组移植瘤大小，检测移植瘤组织中survivin基因的表达。 结果与结论：PAMAM脂质体-survivin-反义寡核苷酸复合物的zeta电位高于PAMAM-survivin-反义寡核苷酸复合物(P < 0.05)，基因包封率两组比较差异无显著性意义(P > 0.05)。PAMAM脂质体-survivin-反义寡核苷酸复合物治疗组裸鼠移植瘤质量及survivin蛋白表达低于PAMAM-survivin-反义寡核苷酸复合物组(P < 0.05)。提示PAMAM脂质体能将Survivin-反义寡核苷酸高效递送到人肝癌移植瘤细胞，降低survivin蛋白的表达，诱导移植瘤细胞凋亡。 关键词：聚酰胺-胺型树枝状高聚合物；脂质体；肝癌；反义寡核苷酸；Survivin doi:10.3969/j.issn.1673-8225.2012.12.020 

Antitumour effects of survivin antisense oligonucleotide carried by polyamidoamine dendrimer liposome on hepatic cancer transplanted subcutaneously in nude mice

BACKGROUND: Antisense oligonucleotide (ASODN) can inhibit survivin expression which induce tumor cell apoptosis. There are still some problems in malignant tumors gene therapy by survivin such as insufficient gene transfer, no long-term stable expression, enzyme degradation. OBJECTIVE: To evaluate the antitumour effects of survivin ASODN carried by polyamidoamine (PAMAM) dendrimer liposome on hepatic cancer transplanted subcutaneously in nude mice.  METHODS: An in vivo model of hepatic cancer was established by injecting SMMC-7721 cells subcutaneously into the flanks of nude mice. The PAMAM dendrimer liposome and PAMAM dendrimer were mixtured with survivin-ASODN respectively to generate the transfection complex. The zeta potential and encapsulating effciency in vitro were determined. When the tumours were palpable, the mixture complex was directly injected into xenografts to observe the size of tumours. The expression of survivin in transplant tumour was measured. RESULTS AND CONCLUSION: The zeta potential of the PAMAM liposome-survivin-ASODN complex was higher than that of the PAMAM-survivin-ASODN complex (P < 0.05). There was no significant difference of envelopment ratio between PAMAM liposome-survivin-ASODN group and PAMAM-survivin-ASODN group (P > 0.05). The expression of survivin protein and weight in transplanted tumours for the PAMAM liposome-survivin-ASODN group were lower than those for PAMAM-survivin-ASODN group  (P < 0.05). The PAMAM dendrimer liposome can delivery surviving ASODN into hepatic transplanted tumour cells effectively, reduce the expression of surviving and induce tumour cells apoptosis.