Summary
Our previous study demonstrated that BM-cyclin 1, a traditional anti-mycoplasma drug, could effectively reverse the multidrug resistance (MDR) of C-A120 cells. The present study aims to explore the reversal effect of BM-cyclin 1 on MDR and its mechanisms in BALB/C nude mice bearing C-A120 cells. Immunoblotting analysis and reverse transcription-polymerase chain reaction (RT-PCR) were used to study the change in multidrug resistance-associated protein 2 (MRP2) induced by BM-cyclin 1. We found that the expression levels of MRP2 protein and mRNA in C-A120 cells treated with BM-cyclin 1 were reduced significantly. Chemical colorimetry revealed no significant change in the level of glutathione (GSH). In the xenograft model, the inhibitory rate of C-A120 cells growth in BM-cyclin 1 plus adriamycin (ADM) group was 52%, which was significantly higher than in control group (P<0.01). The immunoblotting and RT-PCR results conclusively demonstrated that BM-cycin 1 could significantly reduce the expression of MRP2 in transplanted tumor. In conclusion, BM-cyclin 1 could effectively reverse the MDR of C-A120 cells in vivo by suppressing the expression of MRP2.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Tan B, Piwnica-Worms D, Ratner L. Multidrug resistance transporters and modulation. Curr Opi Oncol, 2000, 12(5):450–458
Stepien KM, Tomaszewski M, Tomaszewska J, et al. The multidrug transporter P-glycoprotein in pharmacoresistance to antiepileptic drugs. Pharmacol Rep, 2012, 64(5):1011–1019
Fardel O, Lecureur V, Guillouzo A. The P-glycoprotein multidrug transporter. Gen Pharmacol, 1996,27(8): 1283–1291
Zhang L, Ma S. Efflux pump inhibitors: a strategy to combat P-glycoprotein and the NorA multidrug resistance pump. Chem Med Chem, 2010,5(6):811–822
Kool M, de Haas M, Scheffer GL, et al. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res, 1997,57(16):3537–3547
Abraham I, El Sayed K, Chen ZS, et al. Current status on marine products with reversal effect on cancer multidrug resistance. Mar Drugs, 2012,10(10):2312–2321
Slot AJ, Molinski SV, Cole SP. Mammalian multidrug-resistance proteins (MRPs). Essays in Biochem, 2011,50(1):179–207
Jedlitschky G, Hoffmann U, Kroemer HK. Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol, 2006,2(3):351–366
Sumizawa T, Chuman Y, Sakamoto H, et al. Non-P-glycoprotein-mediated multidrug-resistant human KB cells selected in medium containing adriamycin, cepharanthine, and mezerein. Somat Cell Mol Genet, 1994,20(5):423–435
Wang L, Sun J, Li YQ, et al. Reversal effect of BM-cyclin 1 on multidrug resistance in C-A120 cells. Anti-cancer Drugs, 2007,18(9):1015–1021
Sparreboom A, Danesi R, Ando Y, et al. Pharmacogenomics of ABC transporters and its role in cancer chemotherapy. Drug Resist Updat, 2003,6(2):71–84
Cole SP, Bhardwaj G, Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science, 1992,258(5088):1650–1654
Gottesman MM, Ambudkar SV. Overview: ABC transporters and human disease. J Bioenerg Biomembr, 2001,33(6):453–458
Thomas H, Coley HM. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control, 2003,10(2):159–165
Chen Q, Zhou J, Jiang C, et al. Reversal of P-glycoprotein-mediated multidrug resistance in SGC7901/VCR cells by PPARΓ activation by troglitazone. J Huazhong Univ Sci Technol Med Sci, 2010,30(3):326–331
Bosling J, Poulsen SM, Vester B, et al. Resistance to the peptidyl transferase inhibitor tiamulin caused by mutation of ribosomal protein l3. Antimicrob Agents Chemother, 2003,47(9):2892–2896
Hogenauer G, Ruf C. Ribosomal binding region for the antibiotic tiamulin: stoichiometry, subunit location, and affinity for various analogs. Antimicrob Agents Chemother, 1981,19(2):260–265
Mickisch GH, Multidrug resistance. 18 Mickisch GH, Multidrug resistance. Urologe A, 1996,35(5):370–377
van Zanden JJ, Geraets L, Wortelboer HM, et al. Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells. Biochem Pharmacol, 2004,67(8):1607–1617
Chuman Y, Chen ZS, Seto K, et al. Reversal of MRP-mediated vincristine resistance in KB cells by buthionine sulfoximine in combination with PAK-104P. Cancer Lett, 1998,129(1):69–76
Chen ZS, Mutoh M, Sumizawa T, et al. Reversal of heavy metal resistance in multidrug-resistant human KB carcinoma cells. Biochem Biophys Res Commun, 1997,236(3):586–590
Author information
Authors and Affiliations
Corresponding author
Additional information
The authors contributed equally to this work.
This project was supported by grants from Guangdong Provincial Natural Science Foundation of China (No. S2012010008792) and Fundamental Research Funds for the Central Universities of China (No. 10ykpy05).
Rights and permissions
About this article
Cite this article
Wang, L., Li, X., Jiang, G. et al. Reversal effect of BM-cyclin 1 on multidrug resistance by down-regulating MRP2 in BALB/C nude mice bearing C-A120 cells. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 840–844 (2013). https://doi.org/10.1007/s11596-013-1208-6
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-013-1208-6