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In vitro and in vivo synergetic antitumor effect of c-myc antisense oligodeoxynucleotides combined with 5-fluorouracil
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- Author:
- No author available
- Journal Title:
- JOURNAL OF THE FOURTH MILITARY MEDICAL UNIVERSITY
- Issue:
- 20
- DOI:
- 10.3321/j.issn:1000-2790.2007.20.003
- Key Word:
- 基因,myc;5-氟尿嘧啶;寡核苷酸类,反义;胃肿瘤;体外/体内
Abstract： 目的:探讨c-myc反义寡核苷酸(ASODN)联合5-Fu对胃癌MKN-45细胞株的体内、外抗肿瘤作用.方法:采用脂质体介导c-myc反义寡核苷酸转染人胃癌细胞系,用四甲基偶氮唑盐法(MTT法)评价c-myc ASODN联合5-Fu对胃癌细胞增殖的影响;流式细胞仪(FCM)检测细胞凋亡率和细胞周期;RT-PCR及免疫组化方法检测c-myc基因表达变化;建立荷瘤小鼠模型,通过皮下瘤体内注射药物观察肿瘤体积和抑瘤率的变化.结果:c-myc反义寡核苷酸联合5-Fu可显著抑制细胞增殖,细胞凋亡率(23.4±1.9)%,较单用c-myc反义寡核苷酸(10.6±1.1)%和5-Fu(12.5±1.0)%的抑制作用更为显著(P＜0.01);RT-PCR及免疫组化显示ASODN和5-Fu均使c-myc mRNA和蛋白表达下降;体内实验显示c-myc反义寡核苷酸联合5-Fu可明显减少肿瘤体积,抑制肿瘤生长,抑瘤率达46.7%;较单一治疗组明显(P＜0.05).结论:c-myc基因反义寡核苷酸联合5-Fu能明显抑制胃癌MKN-45细胞增殖、诱导细胞凋亡和下调c-myc蛋白水平;且可有效抑制人胃癌裸鼠皮下肿瘤的生长.
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