Tats Chlich several anticancer agents have been shown to the activity t Pgp in the reporter cells with PXR expression plasmid co hen erh. According to the same anti-cancer drugs Induced expression of Pgp protein in LS180 cells. But when PXR was knocked down in these cells treated with anticancer drugs . Together, Panobinostat LBH-589 these results show that PXR plays an r In the induction of Pgp cancer drug related Important. Additionally there Tzlich Pgp a transporter eZux drug which is involved in the extrusion of a variety of substrates in the cell, wherein the protein of Pgp Evect induction after the treatment with cytostatics in the accumulation set is intracellular Ren Pgp substrates was evaluated. Xutamide docetaxel, paclitaxel and embroidered positive that rifampicin induced expression of proteins aVected Pgp effect the intracellular Re accumulation of rhodamine 123 Pgp substrate.
Moreover found carboplatin and etoposide, which was not on Pgp protein expression Evect not aVect Anh Ufung of rhodamine 123rd However it has been shown, tamoxifen PXR induction mediated activation of protein Pgp but not the aVect Anh Ufung rhodamine 123rd This may be due to the fact that Tamoxifen BMY 7378 also a known inhibitor of Pgp and prevents extrusion Pgp mediated rhodamine 123 erl Explained in more detail. The difference between Pgp protein expression and Pgp function after treatment with the alkaloids of the periwinkle is explained diYcult Ren and requires further investigation. Since the activation of PXR by anticancer agents has been shown that the accumulation of cytotoxic substrates Pgp aVect determine we do whether PXR activation k Nnte also reduce the cytotoxic eVects of doxorubicin, a known Pgp substrate.
However, m Possible pharmacodynamic interactions between cancer drugs doxorubicin and is selected Be selected, leading to increased FITTINGS cytotoxicity t Nnten k Avoid, we have pre-treating the cells with the prototypical PXR agonists rifampicin. For reference chlich reduced pretreatment of cells with LS180 rifampicin intracellular Re accumulation of doxorubicin cytotoxic Pgp substrate and also reduces the eYcacy signiWcantly cytotoxic agent. These results indicate that activation of PXR induction k Pgp-mediated cancer drugs Can the development of acquired resistance to be based. This conclusion is supported by studies of Chen et al. and Gupta et al, who showed that activation of PXR f promotes multidrug-resistant Ph phenotype of prostate and ovarian cancer cell lines.
Since Pgp expressed in tissues with PXR significant obstacles, such as the intestine and liver co, k Nnte the activation of PXR-mediated induction of Pgp aVect proWle the pharmacokinetics of anticancer drugs. Tats Chlich have interactions with other medications drugs have been reported after induction of Pgp-mediated PXR. For example, in St. John, St. John’s wort appeared that contains the PXR agonists hyperforin from healthy subjects Lt Born a first To 9 times in the oral clearance of fexofenadine Pgp substrate, w Entered during rifampicin treatment Born a first 3 to 5 3-fold increase Erh Oral clearance of fexofenadine. Likewise, k Nnten cancer drugs that activate PXR aVect own pharmacokinetics, but also those of other co-administered drugs.