Study on the relationship between breast cancer resistance protein expression and 5-fluorouracil resistance.
- Author:
Jian-Hui YUAN
1
;
Jin-Quan CHENG
;
Yue-Bin KE
;
Na-Na JI
;
Jian-Meng ZHOU
;
Li ZHOU
;
Hai-Yan HUANG
;
Lin-Qing YANG
;
Jian-Jun LIU
;
Xin-Yun XU
;
Zhi-Xiong ZHUANG
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters; genetics; metabolism; Adult; Antimetabolites, Antineoplastic; pharmacology; Breast Neoplasms; drug therapy; metabolism; Drug Resistance, Multiple; genetics; Drug Resistance, Neoplasm; genetics; Female; Fluorouracil; pharmacology; Humans; Middle Aged; Neoplasm Proteins; genetics; metabolism; Tumor Cells, Cultured
- From: Chinese Journal of Preventive Medicine 2008;42(7):506-510
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo screen breast cancer resistance protein BCRP-mediated resistance agents and to investigate the relations between BCRP expression and drug resistance.
METHODSMT assay was performed to screen BCRP-mediated resistant agents with established BCRP expression cell model. While, the high performance liquid chromatography (HPLC) assay was administrated to measure the related dosage of intracellular retention resistant agents. The BCRP expression was investigated by both real-time RT-PCR and immunohistochemistry (IHC) assay in 140 clinical breast cancer tissue specimens. Chemosensitivity to resistant agents for clinical breast cancer tissue specimens was analyzed by MT assay. The Nonparametric variance statistics method was used to analyze the correlations between clinical breast cancer tissue of BCRP expression and drug resistance.
RESULTSMT assay showed that increasing resistance of 5-fluorouracil (5-Fu) climbed with the increases of the BCRP expressions by 10.58 times (P < 0.05, n = 3) in cell model. HPLC assay also proved that a significant negative correlation between the intracellular retention dose of 5-Fu with different expression of BCRP (r = -0.897, P < 0.05, n = 3). Forty-seven tissue specimens of BCRP-positive expression were rapidly determined by using both real-time RT-PCR and IHC in 140 clinical breast cancer tissue specimens. Subsequently, the resistance index (RI) for 47 BCRP-positive clinical breast cancer tissues to 5-Fu was shown from 7 to 12 times compared with normal cancer-side tissues through MT assay. The statistical correlation between BCRP expression and 5-Fu resistance was observed in clinical breast cancer tissue specimens (R2 = 0.8124, P < 0.01).
CONCLUSIONThis study results showed that there is a significant relationship between BCRP expression and 5-Fu resistance. Moreover, the results suggest that the chemotherapy scheme could be optimized on BCRP-positive expression breast cancer patients.