Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells

2011-03-01
Donmez, Yaprak
Gündüz, Ufuk
Purpose: Resistance to anticancer drugs is a serious obstacle to cancer chemotherapy. A common form of multidrug resistance (MDR) is caused by the overexpression of transmembrane transporter proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein-1 (MRP1), encoded by MDR1 and MRP1 genes, respectively. These proteins lead to reduced intracellular drug concentration and decreased cytotoxicity by means of their ability to pump the drugs out of the cells. Breast cancer tumor resistance is mainly associated with overexpression of P-gp/MDR1. Although some chemical MDR modulators aim to overcome MDR by interfering functioning of P-gp, their toxicities limit their usage in clinics. Consequently, RNA interference mediated sequence specific inhibition of the expression of P-gp/MDR1 mRNA may be an efficient tool to reverse MDR phenotype and increase the success of chemotherapy. Aim of this study was resensitizing doxorubicin-resistant breast cancer cells to anticancer agent doxorubicin by selective downregulation of P-gp/MDR1 mRNA.
BIOMEDICINE & PHARMACOTHERAPY

Suggestions

Effect of MDR modulators verapamil and promethazine on gene expression levels of MDR1 and MRP1 in doxorubicin-resistant MCF-7 cells
Donmez, Yaprak; Akhmetova, Laila; Iseri, Ozlem Darcansoy; Kars, Meltem Demirel; Gündüz, Ufuk (2011-04-01)
One of the major problems of cancer chemotherapy is the development of multidrug resistance (MDR) phenotype. Among the numerous mechanisms of MDR, a prominent one is the increased expression of membrane transporter proteins, the action of which leads to decreased intracellular drug concentration and cytotoxicity of drugs. Among them, P-gp and MRP1, encoded by MDR1 and MRP1 genes, respectively, have been associated with MDR phenotype. Chemical modulators can be used to reverse MDR. These chemicals can either...
Reversal of multidrug resistance by synthetic and natural compounds in drug-resistant MCF-7 cell lines
Kars, Meltem Demirel; Iseri, Ozlem Darcansoy; Gündüz, Ufuk; Molnar, Jozsef (2008-01-01)
Background: Ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance (MDR). The purpose of this study is to investigate the potential reversal effect of some synthetic and natural chemicals on drug-resistant MCF-7 cell lines. The effects of potential MDR modulators combined with some anticancer drugs were also studied. Methods: Flow cytometry, MTT cytotoxicity assays and checkerboard combina...
Paclitaxel Resistance in MCF-7/Pac Cell Line is Reversed Successfully by Saikosaponin A and Saikosaponin D
DEMİREL KARS, MELTEM; KARS, GÖKHAN; Gündüz, Ufuk (2013-01-01)
Cancer cells demonstrate multiple drug resistance phenotype frequently after chemotherapy. The resistance of cancer cells to various chemotherapeutic agents is defined as multiple drug resistance. The purpose of this study is to investigate the potential reversal effects of active agents, that are found high amount in plants, on resistant MCF-7 cell lines. The effects of potential MDR modulators combined with anticancer drugs were also evaluated. Flow cytometry, fluorescence microscopy and checkerboard comb...
Reversal of paclitaxel resistance in MCF-7 cell line by achemical modulator elacridar
Şener, Emine Çiğdem; Gündüz, Ufuk; Department of Biology (2012)
The phenomenon called multi drug resistance (MDR) is the resistance of cancer cells to anticancer drugs before or during chemotherapy. One of the mechanisms causing MDR is the upregulation of efflux pumps. The overexpression of MDR1 and MRP1 results in increased efflux of anticancer agents. The aim of this study was to reverse MDR1-mediated paclitaxel resistance in MCF7 breast cancer cell line by a chemical MDR modulator elacridar. In this study, cytotoxicity and the reversal effect of elacridar on sensitiv...
Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Citation Formats
Y. Donmez and U. Gündüz, “Reversal of multidrug resistance by small interfering RNA (siRNA) in doxorubicin-resistant MCF-7 breast cancer cells,” BIOMEDICINE & PHARMACOTHERAPY, pp. 85–89, 2011, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/32661.