多药耐药基因反义寡核苷酸体内逆转耐药的初步研究

Reversal of multidrug resistance with mdr 1 antisense oligodeoxynucleotides in vivo

目的为研究多药耐药（ｍｕｌｔｉｄｒｎｇｒｅｓｉｓｔａｎｃｅＭＤＲ）基因ｍｄｒ１反义寡核苷酸体内逆转肿瘤耐药的作用。方法采用白血病耐药细胞株细胞移植于胸腺缺陷裸小鼠（ＢＡＬＢ／Ｃ）皮下，建立肿瘤耐药模型，局部或腹腔注射ｍｄｒ１反义ＤＮＡ，或以脂质体Ｌｉｐｏｆｅｃｔｉｎ为载体，腹腔注射ｍｄｒ１反义ＤＮＡ，经柔红霉素（ＤＮＲ）和鬼臼乙叉甙（ＶＰ－１６）联合化疗。结果实验组肿瘤生长速度明显低于对照组，从用药后的第５～６天开始，实验组肿瘤体积的增长速率也明显低于相应的对照组，以脂质体为载体的实验组，肿瘤生长出现了暂停的趋势。结论ｍｄｒ１反义寡核苷酸在动物体内具有耐药逆转的作用，脂质体能增强这些作用。

Objective To study the reversal of the multidrug resistance (MDR) in vivo by MDR gene mdr 1 antisense oligodeoxynucleotides. Methods The authors established a model of nude mice which was transplanted with the leukemia resistant cell line HR 20. The mdr 1 antisense oligodeoxynucleotides were injected locally or intraperitoneally or injected with lipofectin. Results After treatment by daunorubincin (DNR) and VP 16 the growth rate of the tumor in the experimental groups significantly slowed down compared with that of controls. After 5 or 6 days of treatment, the speed of growth of tumor′s size also slowed down compared with that of controls. The growth of the tumor tended to suspend temporarily with lipofectin as a vector. Conclusion The results of this study suggested that mdr 1 antisense oligodeoxynucleotides, promoted by lipofectin, played a role in reversal of MDR.