CSB1-Lipo-DOX-miR101靶向治疗乳腺癌及抗耐药效应的体外研究  

CSB1-Lipo-DOX-miR101 targeted therapy of breast cancer and its anti-drug resistance in vitro

作　　者：陈利荣 贾晨霜 冯洋 赵瑞霞 赵雪薇 徐婕 舒展 侯颖春[1] CHEN Lirong;JIA Chenshuang;FENG Yang;ZHAO Ruixia;ZHAO Xuewei;XU Jie;SHU Zhan;HOU Yingchun(School of Life Sciences,Shaanxi Normal University,Xi'an 710119,Shaanxi,China)

机构地区：[1]陕西师范大学生命科学学院,陕西西安710119

出　　处：《陕西师范大学学报（自然科学版）》2023年第3期53-64,共12页Journal of Shaanxi Normal University：Natural Science Edition

基　　金：陕西省自然科学基金(2022JQ-219)。

摘　　要：通过薄膜超声分散技术、硫酸铵主动载药技术构建了靶向乳腺癌(breast cancer,BC)细胞的具有抑制化疗药物多药耐药性(multidrug resistance,MDR)特征的阿霉素(doxorubicin,DOX)脂质体载药体系CSB1-Lipo-DOX-miR101。应用MTT法、损伤修复法、Transwell、细胞核染色、扫描电镜等技术对药物疗效和细胞行为变化进行研究。利用网络数据库分析miRNA101潜在靶向的MDR相关靶基因及BC恶性表征相关基因,以Western blot验证分析miRNA101靶基因的表达及潜在的抗MDR机制。结果表明,CSB1-Lipo-DOX-miR101对BC细胞MCF-7靶向性良好,特别是对耐药性BC细胞MCF-7/ADR具有明显杀伤力,同时对药物的MDR形成具有显著抑制作用,使药物可以持续发挥杀伤作用。结果提示CSB1-Lipo-DOX-miR101可以提高DOX对BC的临床治疗效应、降低毒副作用及复发率,其对BC的治疗效应及对MDR的抑制机理可能是通过抑制ABCC5、EZH2、APEX1、ITGB1、Snail1、MMP2基因表达实现的。The breast cancer(BC)targeting doxorubicin(DOX)liposome drug delivery system CSB1-Lipo-DOX-miR101 with the inhibition for multidrug resistance(MDR)was constructed through thin film ultrasonic dispersion technology and ammonium sulfate active drug loading technology.MTT,wound healing,Transwell,DAPI staining,scanning electron microscopy were used to explore drug efficacy and cell behavior changes.The potential target genes of miRNA101 and BC malignancy relevant genes,as well as the possible anti-MDR mechanism were verified and analyzed by Western blot assay combing data base online assay.The results indicated that CSB1-Lipo-DOX-miR101 targets BC cells accurately,and kills BC cells MCF-7 efficiently,especially DOX resistant BC cells MCF-7/ADR.It showed that the drug delivery can inhibit the formation of MDR,improve therapeutic effect of DOX on BC with reducing toxic side effects,and reduce the recurrence rate of BC.The mechanism of the drug formulation for BC therapy and MDR inhibition may be employed by inhibiting the expression of the ABCC5,EZH2,APEX1,ITGB1,Snail1,MMP2 genes.

关 键 词：乳腺癌 阿霉素 脂质体 靶向药物递送 多药耐药性(MDR) 靶向多肽 miRNA101 

分 类 号：Q28[生物学—细胞生物学]