Reversal of BCRP-mediated multidrug resistance by stable expression of small interfering RNAs

被引：16

作者：

Lv, Hui ^{[1
]}

He, Zhimin ^{[1
]}

Liu, Xiaorong ^{[1
]}

Yuan, Jianhui ^{[1
]}

Yu, Yanhui ^{[1
]}

Chen, Zhuchu ^{[1
]}

机构：

[1] Cent S Univ, Xiangya Med Sch, Canc Res Inst, Hunan, Peoples R China

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2007年 / 102卷 / 01期

关键词：

breast cancer resistance (BCRP); multidrug resistance; RNAi;

D O I：

10.1002/jcb.21276

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Breast cancer resistance protein (BCRP) is an ATP-binding cassette multidrug transporter that confers resistance to various anticancer drugs like Mitoxantrone. Overexpression of BCRP confers multidrug resistance (MDR) in cancer cells and is a frequent impediment to successful chemotherapy. For stable reversal of BCRP-depending MDR by RNA interference technology, a hU6-RNA gene promoter-driven expression vector encoding anti-BCRP short hairpin RNA (shRNA) molecules was constructed. By treating endogenously and exogenously expresses high levels of BCRP cells with these constructs, expression of the targeted BCRP-encoding mRNA, and transport protein was inhibited completely. Furthermore, the accumulation of mitoxantrone in the anti-BCRP shRNA-treated cells increased. And the sensitivity to mitoxantrone of anti-BCRP shRNA-treated cells is increased 14.0-fold and 2.44-fold respectively compared to their control (P< 0.05). These data indicated that stable shRNA-mediated RNAi could be tremendously effective in reversing BCRP-mediated MDR and showed promises in overcoming MDR by gene therapeutic applications. J. Cell. Biochem. 102: 75-81,2007. (C) 2007Wiley-Liss, Inc.

引用

页码：75 / 81

页数：7

共 22 条

[1]

Allikmets R, 1998, CANCER RES, V58, P5337

[2] INTERNAL DUPLICATION AND HOMOLOGY WITH BACTERIAL TRANSPORT PROTEINS IN THE MDR1 (P-GLYCOPROTEIN) GENE FROM MULTIDRUG-RESISTANT HUMAN-CELLS [J].

CHEN, CJ ;

CHIN, JE ;

UEDA, K ;

CLARK, DP ;

PASTAN, I ;

GOTTESMAN, MM ;

RONINSON, IB .

CELL, 1986, 47 (03) :381-389

[3] OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE [J].

COLE, SPC ;

BHARDWAJ, G ;

GERLACH, JH ;

MACKIE, JE ;

GRANT, CE ;

ALMQUIST, KC ;

STEWART, AJ ;

KURZ, EU ;

DUNCAN, AMV ;

DEELEY, RG .

SCIENCE, 1992, 258 (5088) :1650-1654

[4] A multidrug resistance transporter from human MCF-7 breast cancer cells [J].

Doyle, LA ;

Yang, WD ;

Abruzzo, LV ;

Krogmann, T ;

Gao, YM ;

Rishi, AK ;

Ross, DD .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (26) :15665-15670

[5]

Ee PLR, 2004, MOL CANCER THER, V3, P1577

[6] RNA interference is mediated by 21-and 22-nucleotide RNAs [J].

Elbashir, SM ;

Lendeckel, W ;

Tuschl, T .

GENES & DEVELOPMENT, 2001, 15 (02) :188-200

[7] Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans [J].

Fire, A ;

Xu, SQ ;

Montgomery, MK ;

Kostas, SA ;

Driver, SE ;

Mello, CC .

NATURE, 1998, 391 (6669) :806-811

[8] Genetic analysis of the multidrug transporter [J].

Gottesman, MM ;

Hrycyna, CA ;

Schoenlein, PV ;

Germann, UA ;

Pastan, I .

ANNUAL REVIEW OF GENETICS, 1995, 29 :607-649

[9]

HOFFMANN U, 2001, PATHOL RES PRACT, V96, P235

[10] Expression of multidrug resistance-related transporters in human breast carcinoma [J].

Kanzaki, A ;

Toi, M ;

Nakayama, K ;

Bando, H ;

Mutoh, M ;

Uchida, T ;

Fukumoto, M ;

Takebayashi, Y .

JAPANESE JOURNAL OF CANCER RESEARCH, 2001, 92 (04) :452-458

← 1 2 3 →