摘要
目的:探讨聚乙烯亚胺(polyethyleneimine,PEI)介导的生存素(survivin)反义核酸(antisense-oligonu-cleotides,ASODN)联合5-氟尿嘧啶(5-fluorouracil,5-FU)、三氧化二砷(arsenic trioxide)或羟基喜树碱(hydroxy-camptothecine,HCPT)对人肝癌SMMC-7721细胞增殖的抑制作用。方法:单独应用不同浓度的5-FU,As2O3,HCPT,或这些药物分别与survivin ASODN或PEI-ASODN联合应用,作用于SMMC-7721细胞,采用WST-8法检测SMMC-7721细胞的增殖抑制率,并计算药物作用的IC50。以金正均的概率和法进行协同作用分析。结果:不同浓度的5-FU,As2O3或HCPT联合PEI-ASODN(ASODN终浓度为0.125μmol/L)均明显降低这些化疗药物的IC50,提高SMMC-7721细胞对5-FU,As2O3或HCPT的敏感性,增敏倍数分别为36.1、4.16、18.8。金正均Q值法分析表明,5-FU,As2O3或HCPT与PEI-ASODN联合使用,均表现出协同作用。结论:PEI介导的低浓度的生存素反义核酸可提高人肝癌细胞SMMC-7721对5-FU,As2O3和HCPT的敏感性,PEI介导的生存素反义核酸与5-FU联合的作用效果最佳。
Aim：To investigate the inhibitory effects of survivin antisense oligodeoxynucleotide mediated by polyethyleneimine （PEI-ASODN） in combination with 5-fluorouracil （5-FU）, arsenic trioxide （ As2O3 ）, or hydroxy camptothecine （HCPT） on a human hepatocelluar carcinoma SMMC-7721 cell line. Methods： SMMC-7721cells were treated with 5-FU, As2O3, HCPT, or each in combination with survivin antisense oligodeoxynucleotide （ASODN） or PEI-ASODN. The inhibitory rate of cell proliferation was determined by using CCK-8 agent （WST method）, IC50 was calculated, and synergistic effect was evaluated. Results： PEI-ASODN at a dose of 0. 125 μmol/L combined with 5-FU, As2O3 or HCPT all reduced the IC50 of 5-FU, As2O3 or HCPT, and the sensitivity of SMMC-7721 cells to 5-FU, As2O3 or HCPT in the presence of 0. 125μmol/ L PEI-ASODN was enhanced by 36.1, 4. 16, 18.8 times compared with chemotherapeutic drug alone, respectively. Conclusion：Polyethyleneimine -mediated anti- sense oligodeoxynucleotide targeting survivin gene sensitizes SMMC-7721 cells to 5-FU, As203 and HCPT. PEI - ASODN in combination with 5 - FU exerts an optimal anticancer effect in SMMC - 7721, a human hepatocelluar carcinoma.
出处
《暨南大学学报（自然科学与医学版）》
CAS
CSCD
北大核心
2007年第2期147-151,共5页
Journal of Jinan University(Natural Science & Medicine Edition)
基金
广东省医学科研课题(A2002349)
广州市科技计划项目(J1-C0361)
关键词
生存素
反义核酸
肝肿瘤
化学治疗
聚乙烯亚胺
survivin
antisense oligdeoxynucleotides
hepatocellular carcinoma
chemotherapy
polyethyleneimine
