Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Cancer Chemotherapy and Pharmacology
Erschienen 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

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

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 6/2009

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95(26):15665–15670PubMedCrossRef
2.
Schaub V, Hoffmann U, Blohmer JU, Grottke C, Mantwill K, Wichert A, Dietel M, Lage H (1997) Quantitative expression analysis of genes involved in development of chemoresistance in ovarian carcinoma in vitro and in vivo. 4th international symposium on cytostatic drug resistance, Berlin. Band of Abstracts, 96
3.
Ross DD, Karp JE, Chen TT, Doyle LA (2000) Expression of breast cancer resistance protein in blast cells from patients with acute leukemia. Blood 96(1):365–368PubMed
4.
Bessho Y, Oguri T, Achiwa H, Muramatsu H, Maeda H, Niimi T, Sato S, Ueda R (2006) Role of ABCG2 as a biomarker for predicting resistance to CPT-11/SN-38 in lung cancer. Cancer Sci 97(3):192–198PubMedCrossRef
5.
Kanzaki A, Toi M, Nakayama K, Bando H, Mutoh M, Uchida T, Fukumoto M, Takebayashi Y (2001) Expression of multidrug resistance-related transporters in human breast carcinoma. Jpn J Cancer Res 92(4):452–458PubMed
6.
Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD, Miyake K, Resau JH, Bates SE (2000) The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113(Pt 11):2011–2021PubMed
7.
Maliepaard M, van Gastelen MA, de Jong LA, Pluim D, van Waardenburg RC, Ruevekamp-Helmers MC, Floot BG, Schellens JH (1999) Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer Res 59(18):4559–4563PubMed
8.
Nakanishi T, Karp JE, Tan M, Doyle LA, Peters T, Yang W, Wei D, Ross DD (2003) Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res 9:3320–3328PubMed
9.
Lv H, He Z, Liu X, Yuan J, Yu Y, Chen Z (2007) Reversal of BCRP-mediated multidrug resistance by stable expression of small interfering RNAs. J Cell Biochem 102(1):75–81PubMedCrossRef
10.
Yuan JH, He ZM, Yu YH, Chen ZC (2004) Expression establishment and functional analysis of breast cancer resistance protein with doxycycline induced tet regulating system in mouse fibroblast cell line PA317. Ai Zheng 23(10):1127–1133PubMed
11.
Loos WJ, de Bruijn P, Verweij J, Sparreboom A (2000) Determination of camptothecin analogs in biological matrices by high-performance liquid chromatography. Anticancer Drugs 11(5):315–324PubMedCrossRef
12.
Kugawa F, Ueno A, Aoki M (2000) Apoptosis of NG108-15 cells induced by buprenorphine hydrochloride occurs via the caspase-3 pathway. Biol Pharm Bull 23(8):930–935PubMed
13.
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175(1):184–191PubMedCrossRef
14.
Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB (1986) Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47(3):381–389PubMedCrossRef
15.
Cole SP, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AM, Deeley RG (1992) Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258(5088):1650–1654PubMedCrossRef
16.
Borst P, Evers R, Kool M, Wijnholds J (2000) A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst 92(16):1295–1302PubMedCrossRef
17.
Miyake K, Mickley L, Litman T, Zhan Z, Robey R, Cristensen B, Brangi M, Greenberger L, Dean M, Fojo T, Bates SE (1999) Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer Res 59(1):8–13PubMed
18.
Kugawa F, Ueno A, Kawasaki M, Aoki M (2004) Evaluation of cell death caused by CDF (cyclophosphamide, doxorubicin, 5-fluorouracil) multi-drug administration in the human breast cancer cell line MCF-7. Biol Pharm Bull 27(3):392–398PubMedCrossRef
19.
Oshaughnessy JA, Blum J, Moiseyenko V, Jones SE, Miles D, Bell D, Rosso R, Mauriac L, Osterwalder B, Burger HU, Laws S (2001) Randomized, open-label, phase II trial of oral capecitabine (Xeloda) vs. a reference arm of intravenous CMF (cyclophosphamide, methotrexate and 5-fluorouracil) as first-line therapy for advanced/metastatic breast cancer. Ann Oncol 12(9):1247–1254PubMedCrossRef
20.
Rosa DD, Awada A, Cardoso F, Gil T, Lebrun F, Mano MS, Selleslags J, Piccart MJ, D’Hondt V (2007) Oxaliplatin and 5-fluorouracil in heavily pretreated patients with ovarian carcinoma: a well tolerated and efficient treatment. ASCO Meeting Abstracts, vol 25. p 16028
21.
Okamura M, Kobayashi M, Suzuki F, Shimada J, Sakagami H (2007) Induction of cell death by combination treatment with cisplatin and 5-fluorouracil in a human oral squamous cell carcinoma cell line. Anticancer Res 27(5A):3331–3337PubMed
22.
He Z, Yuan J, Chen Z, Liu S, Shen Z, Fei H (1998) Chemosensitivity test for 170 human breast carcinoma samples. Hunan Yi Ke Da Xue Xue Bao 23(6):531–534PubMed
23.
Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH, van De Vijver MJ, Scheper RJ, Schellens JH (2001) Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 61(8):3458–3464PubMed
24.
Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH (2000) Role of breast cancer resistance protein in the bioavailability and fetal penetration of topotecan. J Natl Cancer Inst 92(20):1651–1656PubMedCrossRef
25.
Kruijtzer CM, Beijnen JH, Rosing H, ten Bokkel Huinink WW, Schot M, Jewell RC, Paul EM, Schellens JH (2002) Increased oral bioavailability of topotecan in combination with the breast cancer resistance protein and P-glycoprotein inhibitor GF120918. J Clin Oncol 20(13):2943–2950PubMedCrossRef
26.
Hoffmann U, Materna V, Blohmer JU (2000) Quantitative expression analysis of genes involved in the development of chemoresistance in ovarian carcinoma. Pathol Res Pract 196:235–238
27.
Mao YS, Austin D, Ross DD (2001) BCRP gene expression in normal lung and in non-small cell lung cancer tissue. Chin J Cancer 20:274–278
Metadaten
Titel
Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer
verfasst von
Jianhui Yuan
Hui Lv
Bo Peng
Chengkun Wang
Yanhui Yu
Zhimin He
Publikationsdatum
01.05.2009
Verlag
Springer-Verlag
Erschienen in
Cancer Chemotherapy and Pharmacology / Ausgabe 6/2009
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-008-0838-z

Weitere Artikel der Ausgabe 6/2009

Cancer Chemotherapy and Pharmacology 6/2009 Zur Ausgabe

Original Article

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer

Original Article

Growth inhibitory activity of a novel lectin from Cliona varians against K562 human erythroleukemia cells

Original Article

Statins induce apoptosis in ovarian cancer cells through activation of JNK and enhancement of Bim expression

Original Article

Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant cell lines

Original Article

Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer

Short Communication

Isolated molecular relapse in FIP1L1-PDGFRα hypereosinophilic syndrome after discontinuation and single weekly dose of imatinib: need of quantitative molecular procedures to modulate imatinib dose

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

23.04.2024 Medikamente in Schwangerschaft und Stillzeit Nachrichten

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise