中华医学杂志(英文版)2001,Vol.114Issue(9):929-932,4.
反义寡核柑酸逆转卵巢癌耐药细胞株SKOV3/mdr1耐药性的体外研究
Reversing drug resistance in the ovarian carcinoma cell line SKOV3/mdr1 in vitro by antisense oligodeoxynucleotides
潘凌亚 1童英 1金滢 1杨秀玉 1周生 2张毅 2毛宁2
作者信息
- 1. 中国医学科学院中国协和医科大学北京协和医院妇产科
- 2. 军事医学科学院基础医学研究所细胞生物学实验室
- 折叠
摘要
Abstract
Objective To investigate the effect of multidrug resistance gene 1 (mdr1) antisense oligodeoxynucleotides (ODNs) on reversing multidrug resistance in the drug resistant ovarian carcinoma cell line SKOV3/mdr1.
Methods The ovarian carcinoma cell line SKOV3 transducted with a human multidrug resistance gene (mdr1) served as the drug resistant model (SKOV3/mdr1). The mdr1 antisense ODNs was transfected into SKOV3/mdr1 cells while mediated by lipofectamine. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression and the amount of the mdr1 mRNA in the cells. The positive rate and function of the mdr1 gene product P-glycoprotein (Pgp) in the mdr1 antisense ODNs treated SKOV3/mdr1 cells were determined by flow cytometry and rhodamine 123 efflux. Drug resistance in the SKOV3/mdr1 cell line was observed by MTT assay and cell colony culture.
Results The mdr1 mRNA level was decreased to about 60% of that of β-actin after mdr1 antisense ODNs treatment. The Pgp positive rate of mdr1 antisense ODNs treated SKOV3/mdr1 cells decreased from 100% to 52.6% (P<0.01). The intracellular rhodamine 123 retention was increased from 9.1% to 33.8% (P<0.01). The chemoresistance to taxol decreased to 58% of SKOV3/mdr1 with mdr1 antisense ODN treatment. Compared with SKOV3/mdr1 cells in the control group, under a certain range of drug concentrations, the number of drug resistance colonies in mdr1 antisense ODNs treated SKOV3/mdr1 cells for taxol and doxorubicin decreased by 8.6±0.8 fold and 3.1±0.6 fold, respectively. Some non-specific functions during oligodeoxyncleotide treatment was also detected.
Conclusion mdr1 expression in the SKOV1/mdr1 cell line was partially inhibited after mdr1 antisense ODNs treatment at the mRNA and protein level, increasing the chemotherapy sensitivity of this drug resistant ovarian carcinoma cell line.关键词
寡核柑酸,反义 卵巢肿瘤 耐药性,多药 MDR1基因分类
医药卫生引用本文复制引用
潘凌亚,童英,金滢,杨秀玉,周生,张毅,毛宁..反义寡核柑酸逆转卵巢癌耐药细胞株SKOV3/mdr1耐药性的体外研究[J].中华医学杂志(英文版),2001,114(9):929-932,4.