+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P-glycoprotein-mediated and multidrug-resistance protein-associated multidrug-resistance phenotypes



Comparison of the kinetics of active efflux of 99mTc-MIBI in cells with P-glycoprotein-mediated and multidrug-resistance protein-associated multidrug-resistance phenotypes



European Journal of Biochemistry 252(1): 140-146



The overexpression of two membrane glycoproteins, P-glycoprotein and multidrug-resistance protein (MRP1) is a major cause of resistance to chemotherapeutic agents in the treatment of human cancers. Both proteins confer a similar multidrug-resistant (MDR) phenotype. 99mTc-MIBI, a myocardial imaging agent, which is also useful for the detection of a variety of tumours, has been shown to be a substrate for P-glycoprotein and MRP1. It thus may provide additional information about the P-glycoprotein and MRP1 status of tumour cells. In order to obtain information on the substrate specificity of these proteins, we have studied the transport kinetics of Tc-MIBI in two cell lines, K562/ADR and GLC4/ADR, which overexpress P-glycoprotein and MRP1, respectively. The mean active efflux coefficient ka, which is proportional to the ratio of maximal efflux rate VM to the apparent Michaelis-Menten constant Km, used to characterise the efficiency of the active efflux, was very similar being 1.9 +/- 0.6 x 10(-11) s(-1) x cells x ml and 1.3 +/- 0.5 x 10(-11) s(-1) x cells x ml for drug-resistant K562 and GLC4, respectively. These values are 50-100-times lower than for daunorubicin and other anthracycline derivatives, strongly suggesting that the efficiency of both transporters to pump Tc-MIBI is by far less than that to efflux anthracyclines. Our data show that (a) P-glycoprotein and MRP transporter efficiencies to wash out Tc-MIBI are similar, in spite of a different suspected mechanism of its transport and (b) that both transporters are less efficient to pump Tc-MIBI than to pump anthracyclines (the ka parameter is about 100-times lower for TC-MIBI than for anthracycline).

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 045598131

Download citation: RISBibTeXText

PMID: 9523723

DOI: 10.1046/j.1432-1327.1998.2520140.x


Related references

The Pipecolinate Derivatives VX-710 and VX-853 Are Effective Modulators of Drug Efflux Mediated by the Multidrug Resistance Proteins P-Glycoprotein, Multidrug Resistance Protein and Breast Cancer Resistance Protein in Acute Myeloid Leukemia Cells. Blood 100(11): Abstract No 245, 2002

A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and Mrp-associated multidrug resistance phenotypes. European Journal of Cancer 30(9): 1360-1369, 1994

A comparison of rhodamine 123 accumulation and efflux in cells with P-glycoprotein-mediated and MRP-associated multidrug resistance phenotypes. European Journal of Cancer 30A(9): 1360-1369, 1994

Rhodamine 123 accumulation and efflux in cells with P-glycoprotein -mediated and MRP-associated multidrug resistance phenotypes. Proceedings of the American Association for Cancer Research Annual Meeting 35: 427, 1994

Primary breast cancer imaging with 99mTc-MIBI and expression of the multidrug resistance and multidrug resistance-associated protein. Journal of Nuclear Medicine 42(5 Suppl.): 291P, 2001

Multidrug resistance Relation between the resistance factor, the kinetics of uptake and the kinetics of P-glycoprotein-mediated efflux of various anthracycline derivatives. Abstracts of Papers American Chemical Society 211(1-2): CARB 28, 1996

P-glycoprotein , multidrug-resistance related protein and lung resistance protein multidrug resistance phenotypes in peripheral blood and bone marrow. Proceedings of the American Association for Cancer Research Annual Meeting 38: 388, 1997

Reversal of P-glycoprotein and multidrug resistance-associated protein 1 mediated multidrug resistance in cancer cells by HZ08 Isomers, tetrataisohydroquinolin derivatives. Biological and Pharmaceutical Bulletin 31(6): 1258-1264, 2008

Multifactorial involvement of multidrug resistance-associated [correction of resistance] protein, DNA topoisomerase II and glutathione/glutathione-S-transferase in nonP-glycoprotein-mediated multidrug resistance in human bladder cancer cells. International Journal of Urology 4(6): 583-590, 1997

Relation among the resistance factor, kinetics of uptake, and kinetics of the P-glycoprotein-mediated efflux of doxorubicin, daunorubicin, 8-(S)-fluoroidarubicin, and idarubicin in multidrug-resistant K562 cells. Molecular Pharmacology 49(3): 532-539, 1996

Multidrug resistance modulation by the taxane derivatives IDN-5109 and tRA96023 Effects on P-glycoprotein -, multidrug resistance protein -, and breast cancer resistance protein - mediated drug transport. Proceedings of the American Association for Cancer Research Annual Meeting 43: 950, 2002

99mTc-MIBI imaging as a predictor of therapy response in osteosarcoma compared with multidrug resistance-associated protein and P-glycoprotein expression. Journal of Nuclear Medicine 44(9): 1394-1401, 2003

The activity of latent benzoperimidine esters to inhibit P-glycoprotein and multidrug resistance-associated protein 1 dependent efflux of pirarubicin from several lines of multidrug resistant tumor cells. Cancer Detection and Prevention 28(4): 283-293, 2004

The pipecolinate derivative VX-710 modulates multidrug resistance mediated by P-glycoprotein , multidrug resistance protein and breast cancer resistance protein. Proceedings of the American Association for Cancer Research Annual Meeting 44: 112, 2003

Renal glucuronidation and multidrug resistance protein 2-/ multidrug resistance protein 4-mediated efflux of mycophenolic acid: interaction with cyclosporine and tacrolimus. Translational Research 164(1): 46-56, 2014