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  

Reversal of multidrug resistance of breast carcinoma by antisense oligodeoxynucleotide combined with nanometer particle

作　　者：彭志平[1] 李少林[1] 文明[1] 蒋明东[1] 段红[1] 王树斌[1] 

机构地区：[1]重庆医科大学基础医学院放射医学教研室,重庆400016

出　　处：《第三军医大学学报》2009年第6期498-501,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30070230);重庆市自然科学基金(2007BB5305)~~

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。Objective To explore the reversing effect of antisense oligodeoxynucleotide （ASOND） mediated by nanometer particle against multidrug resistance genes mdr-1 and mrp on the muhidrug resistance of breast cancer cell line MCF-7/ADR. Methods ASOND of mdr-1 and ASODN of mrp were respectively transfeeted 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.

关 键 词：乳腺癌 多药耐药 反义寡脱氧核苷酸 纳米微粒 

分 类 号：R394-33[医药卫生—医学遗传学] R394.6[医药卫生—基础医学]