文章摘要
田国梅赵长久△ 付鹏栾厦张月红吴琼.MDM2 反义寡核苷酸联合紫杉醇对乳腺癌MCF-7 细胞株的作用[J].,2012,12(25):4801-4804
MDM2 反义寡核苷酸联合紫杉醇对乳腺癌MCF-7 细胞株的作用
Effects of MDM2 Antisense Oligonucleotide Combined with Paclitaxelon Human Breast Cancer Cells MCF-7
  
DOI:
中文关键词: MDM2 基因  反义寡核苷酸  紫杉醇  乳腺癌MCF-7 细胞
英文关键词: MDM2 Gene  Antisense Oligonucleotidel  Paclitaxel  Breast Cancer Cell Line MCF-7
基金项目:国家自然科学基金(81171362)
作者单位
田国梅赵长久△ 付鹏栾厦张月红吴琼 哈尔滨医科大学附属第四医院核医学科 
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中文摘要:
      目的:探讨靶向MDM2 反义寡核苷酸(ASON)联合紫杉醇对乳腺癌MCF-7 细胞株的影响。方法:合成一段与MDM2 mRNA 特异性结合的反义寡核苷酸和与反义寡核苷酸有4 个碱基不同的的错义寡核苷酸(MON),脂质体2000 介导不同浓度的MDM2 ASON 转染MCF-7 乳腺癌细胞系,转染的乳腺癌细胞通过1 μmol/L 紫杉醇药物处理后,采用RT-PCR 和Western Blot 方法检测 MDM2 ASON 联合紫杉醇的协同作用及对乳腺癌MCF-7 细胞株的抑制效率,MTT 观察给药后MCF-7 细胞的增殖能力和药物敏 感性。结果:MDM2 反义寡核苷酸联合紫杉醇明显下调MDM2 mRNA 及MDM2 蛋白表达水平,抑制MCF-7 细胞的生长,随着 MDM2 ASON 浓度的增加,MDM2 表达越来越低,协同作用越来越强,呈剂量依赖关系,A500 联合紫杉醇的协同作用最明显, MTT 显示紫杉醇处理的转染MCF-7 细胞增殖抑制率明显增高,A500 抑制增殖作用最明显,抑制率达(13.0±0.84)%。结论:不同 浓度MDM2 ASON 转染后的乳腺癌MCF-7 细胞,等浓度紫杉醇处理后,乳腺癌MCF-7 细胞MDM2 表达明显降低,细胞凋亡增 加,,MDM2 ASON 联合紫杉醇对MCF-7 细胞有协同作用,提高了乳腺癌MCF-7 细胞对紫杉醇的药物敏感性。
英文摘要:
      Objective: To investigate the effects of the MDM2 antisense oligonucleotide (ASON) combined with Paclitaxel on human breast cancer cells MCF-7. Methods: The synthesis of antisense oligonucleotides specific binding of MDM2 mRNA and missense oligonucleotides(MON) different from four bases, different concentrations of MDM2 ASON mediated by Lipofectamine 2000 transfected MCF-7 breast cancer cell lines, breast cancer cells transfected by 1 μmol/L paclitaxel treatment.The expression of MDM2 mRNA and protein was determined by RT-PCR and Western blotting, To detect synergies of MDM2 ASON combined with paclitaxel and the inhibition efficiency of breast cancer cells MCF-7, the proliferation of MCF-7 cell to paclitaxe and chemosensitivity were observed by MTT assay. Results: The antisense oligonucleotide combined with Paclitaxel efficiently down-regulated MDM2 mRNA and protein expression, inhibit the growth ofMCF-7 cells. MDM2 expression was getting lower and lower with the increase of the concentration ofMDM2 ASON growing in a dose dependent relationship, the synergy of the A500 combined with paclitaxel was the most obvious. MTT showed that proliferation inhibition rate of MCF-7 cell transfected to paclitaxel increased significantly, A500 was the most significant effect, inhibition rate was (13.0 ± 0.84)%. Conclusion: Human breast cancer cell MCF-7 transfected was treated by a concentration of paclitaxel, MDM2 expression was significantly decreased, increased apoptosis, MDM2 ASON combined with paclitaxel on MCF-7 cells had a synergistic effect, improved the sensitivity of breast cancer MCF-7 cells to paclitaxel.
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