Pgp inhibition by UIC2 antibody can be followed in vitro by using tumor-diagnostic radiotracers, 99mTc-MIBI and 18FDG
| Autor: | Katalin Goda, Pál Mikecz, Zoltán Hernádi, Zoltán Fodor, Zoárd Tibor Krasznai, Ágnes Tóth, László Galuska, Gábor Szabó |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Technetium Tc 99m Sestamibi
Paclitaxel endocrine system diseases Daunorubicin Glucose metabolic rate Pharmaceutical Science Antineoplastic Agents Biológiai tudományok Biology Pharmacology Rhodamine 123 chemistry.chemical_compound Természettudományok Fluorodeoxyglucose F18 Tumor Cells Cultured polycyclic compounds medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Ovarian Neoplasms integumentary system Antibodies Monoclonal Biological Transport Drug Resistance Multiple female genital diseases and pregnancy complications In vitro carbohydrates (lipids) Multiple drug resistance Glucose chemistry Immunology Cyclosporine biology.protein Female Efflux Antibody Protein Binding medicine.drug |
| Zdroj: | European Journal of Pharmaceutical Sciences. 41:665-669 |
| ISSN: | 0928-0987 |
| Popis: | P-glycoprotein (Pgp, ABCB1) is one of the active efflux pumps that are able to extrude a large variety of chemotherapeutic drugs from the cells, causing the phenomenon of multidrug resistance. It has been shown earlier that the combined application of a class of Pgp modulators (e.g. cyclosporine A and SDZ PSC 833) used at low concentrations and UIC2 antibody is a novel, specific, and effective way of blocking Pgp function (Goda et al., 2007). In the present work we study the UIC2 antibody mediated Pgp inhibition in more detail measuring the accumulation of tumor diagnostic radiotracers, 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) and [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-MIBI), into Pgp(+) (A2780AD) and Pgp(-) (A2780) human ovarian carcinoma cells. Co-incubation of cells with UIC2 and cyclosporine A (CSA, 2μM) increased the binding of UIC2 more than 3-fold and reverted the rhodamine 123 (R123), daunorubicin (DNR) and (99m)Tc-MIBI accumulation of the Pgp(+) 2780AD cells to approx. the same level as observed in Pgp(-) cells. Similarly, 50μM paclitaxel (Pacl) increased UIC2 binding, and consequently reinstated the uptake of R123, DNR and (99m)Tc-MIBI into the Pgp(+) cells. Blocking Pgp by combined treatments with CSA+UIC2 or Pacl+UIC2 also decreased the glucose metabolic rate of the A2780AD Pgp(+) cells measured in (18)FDG accumulation experiments suggesting that the maintenance of Pgp activity requires a considerable amount of energy. Similar treatments of the A2780 Pgp(-) cells did not result in significant change in the R123, DNR, (99m)Tc-MIBI and (18)FDG accumulation demonstrating that the above effects are Pgp-specific. Thus, combined treatment with the UIC2 antibody and Pgp modulators can completely block the function of Pgp in human ovarian carcinoma cells and this effect can be followed in vitro by using tumor-diagnostic radiotracers, (99m)Tc-MIBI and (18)FDG. |
| Databáze: | OpenAIRE |
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