聚乙烯亚胺介导siRNA和顺铂协同抗肿瘤治疗  

Synergistic Antitumor Effect of Cisplatin and siRNA Mediated by Polyethylenimine

作　　者：焦自学[1,2] 陈杰[1] 田华雨[1] 陈学思[1] 

机构地区：[1]中国科学院长春应用化学研究所生态环境高分子材料重点实验室,长春130022 [2]中国科学院大学,北京100049

出　　处：《高分子学报》2015年第1期127-132,共6页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号51303173;51222307;51390480);吉林省科技发展计划项目(基金号20130521011JH)资助

摘　　要：用聚乙烯亚胺(PEI)为载体,介导siRNA(si Survivin)沉默肿瘤细胞抗凋亡基因survivin,并与抗癌药物(顺铂)进行协同抗肿瘤治疗.凝胶阻滞电泳实验显示,PEI能够对siRNA进行有效复合,在PEI/siRNA质量比为0.4时实现完全阻滞.细胞耐药性实验证明了耐顺铂细胞(A549DDP细胞)的survivin基因过度表达且耐顺铂能力是顺铂敏感细胞(A549细胞)的8倍.RT-PCR实验验证了PEI担载si Survivin后对survivin基因实现了有效沉默,与顺铂药物共同作用后不影响基因沉默效果.细胞凋亡实验验证了基因与药物协同作用后细胞的凋亡率达到60.9%,而单独药物或PEI/si Survivin复合物分别作用后的细胞凋亡率仅分别为30.2%和19.8%.细胞增殖实验进一步验证了PEI介导si Survivin与顺铂联合治疗能够实现有效地协同抗肿瘤效果.Polyethylenimine （PEI） was utilized as a carrier for mediating anti-apoptotic siRNA （siSurvivin）, which could silence the expression of survivin gene. The siSurvivin was used with an antitumor drug （cisplatin） for synergistic antituInor treatment. The siRNA binding capacity of PEI was evaluated by gel retardation assay,and the complete formation of PEI/siRNA was achieved at the weight ratio of 0.4. The drug resistant ability was found to be eightfold higher in resistant ceils compared with the sensitive cells, and the survivin gene was overexpressed in A549^DDP cells. RT-PCR experiment proved that PEI/siSurvivin complex was capable of achieving an effective silencing effect of survivin gene,and the silencing effect did not change after the cisplatin was added. Cell apoptosis assay showed that the synergistic effect of cisplatin and gene could achieve a significant apoptosis rate of 60.9% ,while cisplatin or PEI/siSurvivin complex was used alone,only about 30.2% and 19.8% of apoptosis rate could be obtained, respectively. Cell proliferation assays could further validate the effective synergistic antitumor effect of cisplatin and siSurvivin mediated by PEI.

关 键 词：聚乙烯亚胺 SURVIVIN基因 顺铂 协同作用 抗肿瘤 

分 类 号：O631.3[理学—高分子化学] TQ460.1[理学—化学]