|Table of Contents|

MRP1-mediated tumor multidrug resistance

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2016 06
Page:
875-878
Research Field:
Publishing date:

Info

Title:
MRP1-mediated tumor multidrug resistance
Author(s):
Wang Xinping1; Yan Lvnan2
1.Department of General Surgery,Xi'an No.4 Hospital,Shaanxi Xi'an 710004,China;2.Department of General Surgery,West China Hospital,Sichuan University,Sichuan Chengdu 610041,China.
Keywords:
multidrug resistance; multidrug resistance-associated protein; RNA interference
PACS:
R73-3；R730.5
DOI:
10.3969/j.issn.1672-4992.2016.06.007
Abstract:
Objective:To investigate the suppression of MRP1 and MRP1 induced by small interfering RNA and the restoration of sensitivity to chemotherapeutic drugs in the multidrug-resistant hepatocellular carcinoma cell lines HepG2/MRP1.Methods:MRP1-targeted small interfering RNA duplexes were designed,composed and introduced into multidrug-resistant hepatocellular carcinoma cell lines HepG2/MRP1.The suppression of MRP1 mRNA and its gene product MRP1 was examined by RT-PCR and flow cytometry (FCM) respectively. MTT assay was performed to measure the reverse effect of small interfering RNA based on the results of IC50.Results:The overexpression of MRP1 mRNA and MRP1 was suppressed,by the introduction of small interfering RNAs,which caused sequence-specific gene silence.The level of MRP1 mRNA in the transfected HepG2/MRP1 cells reduced to (86.36±2.76) % and MRP1 to (89.38±3.76)% compared with those of the controls. The resistance to ADR was reversed by five folds,which indicated the restoration of sensitivity to drugs.Conclusion:The multidrug resistance of tumors were closely related to the high expression of MRP1. Small interfering RNA can inhibit MRP1 expression and reverse the multidrug resistance mediated by MRP1.

References:

［1］Wang XP,Han L,Li DH,et al.Screening effective sequences of small interfering RNAs targeting MRP1 gene in human HepG2/MRP1 cells［J］.Modern Oncology,2015，23（7）:881-885.［王新平,韩蕾,李德华,等.靶向人多药耐药基因MRP1特异性小分子干扰RNA有效序列筛选［J］.现代肿瘤医学，2015，23（7）:881-885.］
［2］Sun WX,Huang CG.Multidrug resistance: Mechanism and reversal agents［J］.Chemistry of Life,2012,32（5）：395-399.［孙文霞，黄才国.肿瘤多药耐药：机制及逆转剂［J］.生命的化学，2012,32（5）：395-399.］
［3］Chang XB.Molecular mechanism of ATP-dependent solute transport by multidrug resistance-associated protein1［J］.Methods Mol Biot,2010,596:223-249.
［4］Shankar P,Manjunath N,Lieberman J.The prospect of silencing disease using RNA interference［J］.JAMA,2005,293(11):1372－1373.
［5］Borkhardt A.Blocking oncogenes in malignant cells by RNA interference-new hope for a highly specific cancer treatment［J］? Cancer Cell,2002,2:167-168.
［6］Pan GD,Yan LN,Wang XP,et al.Short hairpin RNA/MDR1 reversal of multidrug resistance of hepatocellular carcinoma［J］.Chin J Exp Surg,2007，24（12）：1511-1513.［潘光栋，严律南，王新平，等.短发夹RNA/MDR1逆转肝细胞癌多药耐药［J］.中华实验外科杂志，2007，24（12）：1511-1513.］
［7］Nieth C,Priebsch A,Stege A，et al.Modulation of the classical multidrug resistance (MDR) phenotype by RNA interference (RNAi)［J］.FEBS Lett,2003,545(2-3):144-150.
［8］Ee PL,He X,Ross DD,et al.Modulation of breast cancer resistance protein (BCRP/ABCG2) gene expression using RNA interference［J］.Mol Cancer Ther,2004,3(12):1577-1583.
［9］Rumpold H,Wolf AM,Gruenewald K,et al.RNAi-mediated knockdown of P-glycoprotein using a transposon-based vector system durably restores imatinib sensitivity in imatinib-resistant CML cell lines［J］.Exp Hematol,2005,33(7):767-775.

Memo

Memo:
-
Last Update: 2016-01-29