【摘要】 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48h后细胞耐药基因mdr-1、mrp的表达;MTT法检测经转染后MCF-7/ADR细胞对阿霉素(ADR)、表柔比星(epirubicin)、5-氟脲嘧啶(5-FU)和紫杉醇(paclitaxel)的敏感性。结果纳米微粒介导mdr-1、mrpASODN转染48h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(P<0.05);细胞对ADR、表柔比星、5-氟脲嘧啶和紫杉醇的耐药指数均显著降低(P<0.05)。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。更多还原

【Abstract】 Objective To explore the reversing effect of antisense oligodeoxynucleotide (ASOND) mediated by nanometer particle against multidrug resistance genes mdr-1 and mrp on the multidrug resistance of breast cancer cell line MCF-7/ADR. Methods ASOND of mdr-1 and ASODN of mrp were respectively transfected into MCF-7/ADR cells by nanometer particle. Their sense oligodeoxynucleotides were also transduced to serve as control. The changes of mdr-1 and mrp expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting in 48 h after transfection. MTT assay were performed to evaluate the sensibility of the transfected cells to adriamycin, epirubicin, 5-fluorouracil and paclitaxel respectively. Results After 48 hours’ exposure to mdr-1-ASODN or mrp-ASODN mediated by nanometer particle, MCF-7/ADR cells significantly reduced the expressions of mdr-1 and mrp in mRNA and protein levels (P<0.05), and enhanced drug sensitivity to adriamycin, epirubicin, 5-fluorouracil and paclitaxel respectively (P<0.05). Conclusion ASOND enhances the drug sensitivity of breast cancer cell line MCF-7/ADR by inhibiting the expressions of drug resistance genes. Nanometer particle is a valid tool to mediate ASOND in vitro.更多还原