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Cancer Chemotherapy and Pharmacology

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01.10.2009 | Original Article

Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function

verfasst von: Li-yang Tao, Yong-ju Liang, Fang Wang, Li-ming Chen, Yan-yan Yan, Chun-ling Dai, Li-wu Fu

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2009

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Abstract

Purpose

Cediranib (recentin, AZD2171) is an oral small-molecule multiple receptor tyrosine kinases inhibitor. Here we investigate the ability of cediranib to reverse tumor multidrug resistance (MDR) due to overexpression of ABCB1 (P-glycoprotein) and ABCC1 (MRP1) transporters.

Methods

KBv200,MCF-7/adr, C-A120 and their parental sensitive cell lines KB, MCF-7 and KB-3-1 were used for reversal study. The intracellular accumulations of doxorubicin and rhodamine 123 were determined by flow cytometry. The expressions levels of ABCB1 and ABCC1 were investigated by Western blot and RT-PCR analyses. ATPase activity assay were performed by Luminescence. The functions of ERK in MCF-7/adr were investigated by RNA interference.

Results

Cediranib significantly enhanced the sensitivity of ABCB1 or ABCC1 substrates in MDR cells, with no effect found on sensitive cells. However, the expressions of these transporters were not affected and the reversal activity of cediranib was not related to the phosphorylation of AKT or ERK1/2. Further studies showed that cediranib inhibited ATPase activity of ABCB1 (P-glycoprotein) in a dose-dependent manner.

Conclusions

Cediranib reverses ABCB1- and ABCC1-mediated MDR by directly inhibiting their drug efflux function. These findings may be useful for cancer combinational therapy with cediranib in the clinic.

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Titel: Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function
verfasst von: Li-yang Tao
Yong-ju Liang
Fang Wang
Li-ming Chen
Yan-yan Yan
Chun-ling Dai
Li-wu Fu
Publikationsdatum: 01.10.2009
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-009-0949-1

Springer Medizin

Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function

Abstract

Purpose

Methods

Results

Conclusions

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Update Onkologie

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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