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ATP7B siRNA阳离子纳米脂质体逆转卵巢癌细胞株顺铂耐药的体内外实验研究

钱艺美 王军青 周闺臣 陈菡

实用妇产科杂志2012,Vol.28Issue(12):1030-1034,5.
实用妇产科杂志2012,Vol.28Issue(12):1030-1034,5.

ATP7B siRNA阳离子纳米脂质体逆转卵巢癌细胞株顺铂耐药的体内外实验研究

The Reversal of Cisplatin Resistance in an Ovarian Cancer Cell Line by Cationic Liposomes Loaded with ATP7B Small Interfering RNA

钱艺美 1王军青 1周闺臣 2陈菡2

作者信息

  • 1. 解放军第101医院,江苏无锡214000
  • 2. 第二军医大学药学院,上海200433
  • 折叠

摘要

Abstract

Objective: The aim of this study was to investigate the effect and mechanism of the reversal of Cisplatin (DDP) resistance in an ovarian cancer cell line by cationic liposomes loaded with ATP7B small interfering RNA (siRNA) (ATP7B/DC-Lip). Methods:A SKOV3 ovarian cancer cell line which is resistant to DDP (SKOV3/DDP) was developed by a gradient induction method with DDP. Cell proliferation assays were used to determine the resistance index of SK0V3/DDP. Furthermore, ATP7B/DC-Lip was developed by a thin-film method,and the size and encapsulation efficiency of siRNA of ATP7B/DC-Lip were measured. Cell proliferation assays and in vivo antitumor assays were performed to evaluate the in vitro and in vivo antitumor activity of reagents. Results:SKOV3/DDP was successfully developed by a gradient induction method with DDP,ATP7B/DC-Lip could significantly silence the protein expression of ATP7B. The cell proliferation assay showed that ATP7B/DC-Lip significantly reversed the DDP resistance of SKOV3/DDP,with a much reduced IC50 of 3. 51 ± 0. 93 μg/ml (n =6). Furthermore,ATP7B/DC-Lip combined with DDP significantly inhibited the tumor development and possessed the best antitumor activity compared with other three groups (negative control,ATP7B/DC-Lip and DDP) (P<0. 05). Conclusions:ATP7B/DC-Lip could significantly reverse the DDP resistance of SKOV3/DDP both in vitro and in vivo, suggesting that it may serve as an effective nanomedicine in treating ovarian cancer with DDP resistance.

关键词

卵巢癌/耐药/肿瘤治疗/P型铜转运ATP酶/小干扰RNA

Key words

Ovarian cancer/ Drug resistance/ Tumor therapy/Copper-transporting ATPase 2/ Small interfering RNA (siRNA)

分类

医药卫生

引用本文复制引用

钱艺美,王军青,周闺臣,陈菡..ATP7B siRNA阳离子纳米脂质体逆转卵巢癌细胞株顺铂耐药的体内外实验研究[J].实用妇产科杂志,2012,28(12):1030-1034,5.

实用妇产科杂志

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