超声造影剂联合超声介导耐药基因反义寡脱氧核苷酸转染肝癌细胞逆转多药耐药效应的研究

Research in QGY/CDDP hepatoma lines multi-drug resistance reversed by ultrasound contrast agent joint ultrasound mediating ASODN of drug resistance gene transfection

目的探讨超声造影剂联合超声介导mdr1、mrp基因反义寡脱氧核苷酸（ASODN）转染QGY耐药肝癌细胞对多药耐药（MDR）的逆转。方法分别将mdr1、mrp-ASODN＋超声造影剂＋超声辐照转染QGY／CDDP肝癌细胞，检测转染后细胞贴壁率、药物敏感性、耐药基因mRNA表达和相应耐药蛋白表达变化。结果mdr1—ASODN转染后，细胞贴壁率和耐药基因mRNA表达变化大（P〈0．05），细胞药物敏感性和耐药蛋白P-gp、MRP表达变化小（P〉0．05）。实验组（2组）作用更大（P〈0．05）。mrp—As0DN转染后，细胞贴壁率、药物敏感性、耐药基因的mRNA表达和耐药蛋白P-gp、MRP表达均变化明显（P〈（）．05），实验组（2组）作用更大（P〈0．05）。结论mdrl、mrp—ASODN＋超声造影剂＋超声辐照能够低毒部分逆转肝癌细胞MDR，是潜在肿瘤基因治疗方法。

Objective To discuss the effect of QGY/CDDP hepatoma lines multi-drug resistance （MDR） reversed by gene transfection of mdrl, mrp-ASODN ＋ ultrasound contrast agent ＋ ultrasound. Methods The QGY/CDDP cells were transfected by mdrl, mrp-ASODN ＋ ultrasound contrast agent ＋ ultrasound irradiation respectively and detected of the various indicators：cell adhesion rate,cell sensitivity to cell drug-resistance, the mRNA expression of mdrl and mrp gene, the expression of P-gp and MRP protein. Results After mdrl-ASODN transfection, the drug sensitivity and expression of P-gp, MRP protein of QGY/CDDP cells were smaller changes（ P 〉0.05） ,and the rate of cells adherent and expression of resistance gene mRNA were obvious changes （P 〈 0. 05）. After mrp-ASODN transfection, the cells adherent rate, the drug sensitivity, the expression of resistance gene mRNA and P-gp, MRP protein were obvious changes respectively（ P 〈0.05 ）, the experiment group（group 2＇） had bigger effects（ P 〈0.05 ）. Conclusions mdrl, mrp-ASODN ＋ ultrasound contrast agent ＋ ultrasound irradiation could safely partly reverse MDR of hepatoma cells,which is a potential new approach for gene therapy.