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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2009

01-05-2009 | Original Article

Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer

Authors: Jianhui Yuan, Hui Lv, Bo Peng, Chengkun Wang, Yanhui Yu, Zhimin He

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2009

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Abstract

Purpose

Chemotherapy is not only important but also necessary for the patient of breast cancer. Breast cancer resistance protein (BCRP), an atypical drug efflux pump, mediates multidrug resistance in breast cancer. The aim of this study is to search new substrate of BCRP. The result will guide the drug selection of chemotherapy in BCRP-positive breast cancer.

Methods

PA317/Tet-on/TRE-BCRP cell induced with doxycycline was used to screen the possible substrates of BCRP by MTT assay. The suspicious substrate [5-fluorouracil (5-Fu)] was further confirmed in PA317 and breast cancer cell MCF-7 by HLCP, apoptosis assay (staining and FACS) and RNAi technique.

Results

Mitoxantrone, 5-Fu, adriamycin, Methotrexate, Pirarubicin, and Etoposide were identified as substrates of BCRP. However, Paclitaxel, Vincristine, Vindesine, Mitomycin C, and cisplatin were not mediated by BCRP. 5-Fu was identified as substrate of BCRP for the first time. The further study showed that the intracellular retention dose of 5-Fu and the 5-Fu induced cellular apoptosis all decreased when BCRP highly expressed. Furthermore, 5-Fu accumulation and 5-Fu induced DNA damage increased when BCRP was silenced by RNAi in breast cancer cells.

Conclusions

5-Fluorouracil may be a specific substrate which can be bound by BCRP. BCRP can predict the sensitivity of breast cancer to 5-Fu. And BCRP-targeted therapy will reverse the resistance of breast cancer to 5-Fu.
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Metadata
Title
Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer
Authors
Jianhui Yuan
Hui Lv
Bo Peng
Chengkun Wang
Yanhui Yu
Zhimin He
Publication date
01-05-2009
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2009
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0838-z

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