Transport mechanism of bergenin aross MDCK-MDRl cell monolayer model / 中国药理学通报

Aim To study the transport mechanism of bergenin passing through blood-brain barrier ( BBB ) . Methods MTT assay was used to investigate the tox-icity of bergenin on MDCK-MDRl cells. Molecular docking was used to predict the binding mode and effect ability of bergenin with P-gp. In vitro MDCK-MDRl cell monolayer model was used to analyze trans¬port characteristics of bergenin and the effect of con¬centration, time and verapamil (a P-gp inhibitor) on the transport of bergenin. Results Bergenin was non-toxic to MDCK-MDRl cells within the concentration of 5 to 40 jjunol • L . There was hydrogen-bond and hy-drophobic interaction between P-gp and bergenin, and P-gp-bergenin was more stable than P-gp-verapamil. The P value of bergenin transported from AP to BL (PappAP

Imaging Multidrug Resistance in Hematological Malignancies.

In hematological malignancies, multidrag resistance (MDR) has been associated with the drag efflux pumps: one is the classical Mr 170,000 P-glycoprotein (Pgp) and the other Mr 190,000 multidrag resistance-associated protein (MRP). In addition, the overexpression of a recently identified protein, lung resistance protein (LRP), is also associated with reduced intracellular drag accumulation and retention. Currently available detection methods may provide variable results among laboratories, as there is no single set of standards for detection techniques at the mRNA or protein level. Moreover, these methods may not be informative about the in vivo function of Pgp, MRP or LRP. Single-photon emission tomography (SPECT) and positron emission tomography (PET) have been evaluated for the non-invasive determination of Pgp- and MRP- mediated transport systems. Tc-99m-hexaxis-2-methoxyisobutyl isonitrile (Tc-99m-Sestamibi), an agent used in myocardial perfusion and tumor imaging, is a substrate for Pgp and MRP, and has been used for tumor imaging, and to visualize Pgp expression. Tc-99m-Tetrofosmin and several Tc-99m-Q complexes, are also recognized as substrates by Pgp pump mechanism. Moreover, radiopharmaceuticals including carbon-11-labeled colchicine, verapamil and daunorabicin have been used for the assessment of Pgp-mediated transport functions in vivo using PET technology. The results suggest that the potential exists for nuclear medicine imaging using either Tc-99m-labeled compounds and SPECT or carbon-11-labeled compounds and PET to detect MDR in tumors prior to or after exposure to chemotherapeutic agents.