纳米微粒介导反义寡脱氧核苷酸逆转乳腺癌细胞多药耐药的实验研究.docVIP

文章编号：1000-5404(2008) 纳米微粒介导反义寡脱氧核苷酸逆转乳腺癌细胞多药耐药的实验研究 彭志平，李少林，文 明，蒋明东，段 红，王树斌 （重庆医科大学基础医学院放射医学教研室，重庆 400016） 提 要： 目的 探讨纳米微粒介导耐药基因mdr-1、mrp反义寡脱氧核苷酸（antisense oligodeoxynucleotide, ASODN）转染对多药耐药乳腺癌MCF-7/ADR细胞的影响。方法 采用纳米微粒介导mdr-1、mrp-ASODN转染耐药细胞株MCF-7/ADR，RT-PCR、Western blot检测转染48 h后细胞耐药基因mdr-1、mrp的表达；MTT法检测经转染后MCF-7/ADR细胞对（ADR）、表柔比星（epirubicin）、5-（5-Fu）紫杉醇（paclitaxel）的敏感性。结果 纳米微粒介导mdr-1、mrp ASODN转染48 h后，MCF-7/ADR细胞的mdr-1、mrp在mRNA和蛋白质表达水平上均显著降低（P0.05）；细胞对ADR、epirubicin、5-Fupaclitaxel的耐药指数均显著降低（P0.05）。结论 耐药基因反义寡脱氧核苷酸能在体外抑制耐药基因的表达，从而提高细胞的药物敏感性；纳米微粒具有较好的体外介导反义寡脱氧核苷酸转染效果。 乳腺癌；多药耐药；反义寡脱氧核苷酸；纳米微粒Reversal of multidrug resistance of breast carcinoma by antisense oligodeoxynucleotide combined with nanometer particle PENG Zhi-ping, LI Shao-lin, WEN Ming, JIANG Ming-dong, Duan Hong, WANG Shu-bing (Department of Radiation Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China) Abstract: Objective To explore the reversing effect of multidrug resistance on breast cancer cell line MCF-7/ADR with mdr-1 and mrp antisense oligodeoxynucleotide mediated by nanometer particle. Methods mdr-1 and mrp antisense oligodeoxynucleotide were transfected into MCF-7/ADR cells by nanometer particle. The changes of the expression of mdr-1 and mrp were detected by reverse transcription-polymerase chain reaction and western blot at 48h. MTT assay were performed to evaluate the sensibility of the transfected cells to adriamycin, epirubicin, 5-fluorouracil and paclitaxel. Results After 48 hours of exposure to mdr-1 ASODN or mrp-ASODN mediated by nanometer particle, MCF-7/ADR cells significantly reduced the express of mdr-1 and mrp, both in mRNA and protein(P0.05), and enhanced drug sensitivity to adriamycin, epirubicin, 5-fluorouracil and paclitaxel(P0.05). Conclusion Antisense oligodeoxynucleotide can enhance drug sensitivity by inhibiting the express of drug resistance gene and nanometer particle is a valid tool on mediating antisense oligodeoxyribonu