核酶对人肺腺癌细胞多药耐药的逆转

目的 探讨针对多药耐药基因（ｍｄｒｌ）的核酶对肺腺癌细胞多药耐药的逆转作用。方法以ｍｄｒｌ ｍＲＮＡ ８８０位点为靶位点，通过脂质介导，将抗ｍｄｒｌ核酶表达质粒（ｐＨ β Ａｐｒ－ｌ ｎｅｏ／ｍｄｒｌ－Ｒｂ）导入肺腺癌耐药细胞株Ａ５４９／Ｒ。分别采用ＲＴ－ＰＣＲ、流式细胞仪检测术、罗丹明聚集及ＭＴＴ方法，观察细胞的ｍｄｒｌ ｍＲＮＡ、Ｐ糖蛋白（Ｐ－ｇｌｙｃｏｐｒｏｔｅｉｎ，Ｐｇｐ）表达和对阿霉素敏

Reversion of multidrug resistance in vitro of lung adenocarcinoma by mdr1 ribozyme

OBJECTIVE: To investigate the possibility of reversion of multidrug resistant (MDR) in lung adenocarcinoma-resistant cell line A549/R by mdr1 ribozyme. METHODS: With GUC at 880 site of mdr1 mRNA selected as target point, plasmid expressing mdr1 ribozyme (pH beta Apr-1 neo/mdr1-Rb) was transduced to A549/R by lipofectin. The expression of mdr1 mRNA and Pgp, cellular rhodamine accumulation and sensitivity to doxorubicin were examined in ribozyme transduced and non-transduced cells. RESULTS: Transduction of mdr1 ribozyme to A549/R cells led to decrease in mdr1 mRNA and Pgp expression; increase in rhodamine accumulation. The sensitivity of the ribozyme transduced cells to doxorubicin was 200-fold as high as that of the parental drug-resistant cells. CONCLUSION: MDR of lung adenocarcinoma-resistant cell line A549/R can be effectively reversed with mdr1 ribozyme by cleavage of mdr1 mRNA and inhibition of Pgp expression.