Summary
The roles of multi-drug resistance protein 1 (MDR1), multi-drug resistance related protein 1 (MRP1), lung resistance protein (LRP) and breast cancer resistance protein (BCRP) in the multi-drug resistance (MDR) of hepatocellular carcinoma (HCC) were studied. By exposing HepG2 cell line to progressively increased concentrations of adriamycin (ADM), HepG2 multi-drug resistant subline (HepG2/ADM) was induced. The MDR index of HepG2/ADM was detected by using MTT. The expressions of the four MDR proteins in the three cell lines (L02, HepG2, HepG2/ADM) were investigated at mRNA and protein levels by real-time RT-PCR and Western blot respectively. Our results showed that when the ADM concentration was under 100 μg/L, HepG2 could easily be induced to be drug-resistant. The IC50 of the HepG2/ADM to ADM was 282 times that of HepG2. The expression of MDR1 and BCRP mRNA in HepG2/ADM cells were 400 and 9 times that of HepG2 cells respectively while there was no difference in the mRNA expressions of MRP1 and LRP. There was no difference between HepG2 and L02 cells in the mRNA expressions of the four genes. At the protein level, the expressions of MDR1, BCRP and LRP but MRP1 in HepG2/ADM were significantly higher than those of HepG2 and L02. Between HepG2 and L02, there was no difference in the expressions of four genes at the protein level. HepG2/ADM is a good model for the study of MDR. The four genes are probably the normally expressed gene in liver. The expressions of MDR1 and BCRP could be up-regulated by anti-cancer agents in vitro. The MDR of HCC was mainly due to the up-regulation of MDR1 and BCRP but MRP1 and LRP. These findings suggest they may serve as targets for the reversal of MDR of HCC.
Similar content being viewed by others
References
Doyle L A, Yang W, Abruzzo L V et al. A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A, 1998,95(26):15665–15670
Uggla B, Stahl E, Wagsater D et al. BCRP mRNA expression v. clinical outcome in 40 adult AML patients. Leuk Res, 2005,29(2):141–146
Abbott B L, Colapietro A M, Barnes Y et al. Low levels of ABCG2 expression in adult AML blast samples. Blood, 2002, 100(13):4594–4601
van der Kolk D M, Vellenga E, Scheffer G L et al. Expression and activity of breast cancer resistance protein (BCRP) in de novo and relapsed acute myeloid leukemia. Blood, 2002, 99(10):3763–3770
Ding L, Chen X P, Zhang Z W et al. Study on the mechanism of reversing multidrug resistance of hepatocarcinoma by bromocriptine. Zhonghua Gan Zang Bing Za Zhi, 2006, 14(5):353–357
Brugger D, Brischwein K, Liu C et al. Induction of drug resistance and protein kinase C genes in A2780 ovarian cancer cells after incubation with antineoplastic agents at sublethal concentrations. Anticancer Res, 2002,22(6C):4229–4232
Volk E L, Farley K M, Wu Y et al. Overexpression of wild-type breast cancer resistance protein mediates methotrexate resistance. Cancer Res, 2002,62(17):5035–5040
Kowalski P, Stein U, Scheffer G L et al. Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2. Cancer Gene Ther, 2002,9(7):579–586
Merino G, van Herwaarden A E, Wagenaar E et al. Sex-dependent expression and activity of the ATP-binding cassette transporter breast cancer resistance protein (BCRP/ABCG2) in liver. Mol Pharmacol, 2005,67(5):1765–1771
Suvannasankha A, Minderman H, O’Loughlin K L et al. Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function. Leukemia, 2004,18(7):1252–1257
Tahara H, Kusuhara H, Fuse E et al. P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion. Drug Metab Dispos, 2005,33(7):963–968
Author information
Authors and Affiliations
Additional information
LI Gaopeng, male, born in 1981, Doctor in Charge
This project was supported by a grant from the Foundation for Key Scientific Research Programs of Ministry of Health of China (No. 2001–2003).
Rights and permissions
About this article
Cite this article
Li, G., Chen, X., Wang, Q. et al. The roles of four multi-drug resistance proteins in hepatocellular carcinoma multidrug resistance. J. Huazhong Univ. Sc. Technol. 27, 173–175 (2007). https://doi.org/10.1007/s11596-007-0217-8
Received:
Issue Date:
DOI: https://doi.org/10.1007/s11596-007-0217-8