纳米载体介导的hTERT反义寡核苷酸对A549细胞抑制作用研究

发布时间：2018-01-05 14:22

本文关键词：纳米载体介导的hTERT反义寡核苷酸对A549细胞抑制作用研究　出处：《郑州大学》2005年硕士论文　论文类型：学位论文

更多相关文章： 纳米粒 hTERT 反义寡核苷酸 A549细胞

【摘要】：端粒(telomere)是位于真核细胞线性染色体末端的天然结构,对于保护染色体、防止染色体融合、降解是非常重要的。随着正常细胞的分裂,端粒的长度逐渐缩短,最终导致细胞的衰老、死亡。在绝大多数真核细胞中,通过一种特殊的酶即端粒酶(telomerase)来合成端粒DNA重复序列。端粒酶是一种核蛋白,它利用其自身RNA组分为模板,通过在染色体末端增加(TTAGGG)n重复序列来补偿端粒的缩短。大多数肿瘤细胞能通过表达端粒酶活性而维持其端粒长度,端粒酶的表达在细胞永生化及癌变过程中起重要作用。研究表明,在80%～85%肺癌组织中检测到端粒酶阳性,而在癌旁正常组织几乎均为阴性,表明端粒酶的激活在肺癌的发生发展中起重要作用。端粒酶逆转录酶(human telomerase reverse transcriptase,hTERT)是端粒酶的催化亚单位,是端粒酶活性的限速决定因素。近年来许多研究表明,hTERT的表达与端粒酶活性相一致,因此,hTERT mRNA成为端粒酶活性抑制的理想靶点。利用反义核酸技术,人工合成靶向hTERT的反义寡核苷酸(Antisense oligodeoxynucleotides,ASODN),抑制hTERT mRNA表达和端粒酶活性,诱导肿瘤细胞凋亡,是目前进行肿瘤基因治疗的方向之一。为了克服反义核酸易被核酸酶降解的缺点,常常采用硫代修饰反义核酸的方法,但硫代修饰价格昂贵,难以在临床应用。随着纳米技术的发展,利用纳米粒作为载体,能够很好地解决反义核酸被核酸酶降解的问题,并可改善细胞吞噬,提高反义核酸在细胞内的稳定性,
[Abstract]:Telomere length (telomere) is a natural structure located at the ends of eukaryotic chromosomes, to protect chromosome, prevent chromosome fusion, the degradation is very important. With the normal cell division, telomere length is shortened gradually, eventually leading to cell senescence, death. In most eukaryotic cells, through a special enzyme telomerase (telomerase) synthesis of telomeric DNA repeats. Telomerase is a ribonucleoprotein, it uses its RNA component as a template, by adding on the ends of chromosomes (TTAGGG) n repeat sequence to compensate for telomere shortening. Most of the tumor cells can maintain telomere length through the expression of telomerase activity, telomerase expression an important role in cell immortalization and carcinogenesis. The results show that in the 80% to 85% lung cancer detected in telomerase positive, while in the adjacent normal tissues were almost negative, that end The activation of telomerase plays an important role in the development of lung cancer. Telomerase reverse transcriptase (human telomerase reverse transcriptase, hTERT) is the catalytic subunit of telomerase, telomerase activity is the rate limiting determinant. Many studies show that in recent years, consistent expression and telomerase activity of hTERT so hTERT mRNA an ideal target some inhibition of telomerase activity.
The use of antisense technology, synthetic antisense oligonucleotide targeting hTERT (Antisense, oligodeoxynucleotides, ASODN, mRNA) inhibited the expression of hTERT and telomerase activity and induce apoptosis of tumor cell, is one of the directions of tumor gene therapy. In order to overcome the antisense nucleic acid susceptible to nuclease degradation shortcomings, often using antisense nucleic acid method phosphorothioate, but phosphorothioate is expensive, difficult in clinical application. With the development of nanotechnology, the use of nanoparticles as carrier, can be solved by antisense nucleic acid nuclease degradation problems, and can improve the phagocytic cells, improve the stability of antisense RNA in cells,

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R346;R734.2

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