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目的探讨体内、体外mdr1、mrp、lrp反义寡核苷酸(AODNs)并超声微泡造影剂转染联合低强度超声照射逆转肝癌多药耐药的可行性,寻找逆转肿瘤多药耐药有效和靶向的方法。方法利用超声微泡造影剂包载肿瘤耐药基因mdr1、mrp、lrp的AODNs进行转染,联合低强度超声照射,以肝癌细胞多药耐药细胞模型(HepG2／ADM) 为研究对象,通过逆转录聚合酶链反应、western blot和四甲基偶氮唑盐法,从体外细胞培养及动物实验,研究 AODNs并超声微泡造影剂转染联合超声照射逆转癌细胞多药耐药及降低肿瘤恶性表型和成瘤能力的作用。结果 HepG2／AMD细胞增殖被抑制,其mdr1和mrp的mRNA、蛋白质表达水平明显降低;裸鼠皮下移植瘤生长受抑制。结论体外、体内AODNs并超声微泡造影剂转染联合低强度超声照射能有效逆转人肝癌细胞HepG2／ADM的多药耐药, 该技术可能为肝癌临床治疗提供新的思路。
Objective To investigate the feasibility of reversing the multidrug resistance of hepatocellular carcinoma with mdr1, mrp, lrp antisense oligodeoxynucleotides (AODNs) in vitro and in vivo and ultrasound microbubble contrast agent transfection in combination with low intensity ultrasound irradiation. And targeted methods. Methods AODNs containing mdr1, mrp and lrp were packaged by ultrasound microbubble contrast medium and combined with low intensity ultrasound irradiation. HepG2 / ADM cells were treated by reversal Polymerase chain reaction, western blot and tetramethylzirconate method were used to study the effects of AODNs and ultrasound microbubble contrast agent transfection combined with ultrasound irradiation on the multidrug resistance of cancer cells and the reduction of malignancy The role of phenotype and tumorigenicity. Results The proliferation of HepG2 / AMD cells was inhibited and the mRNA and protein expressions of mdr1 and mrp were significantly decreased. The growth of subcutaneous xenografts in nude mice was inhibited. Conclusion In vitro and in vivo AODNs combined with ultrasound microbubble contrast agent transfection combined with low intensity ultrasound irradiation can effectively reverse multidrug resistance of HepG2 / ADM human hepatoma cells. This technique may provide a new idea for the clinical treatment of liver cancer.