Author(s)

S. Seddiki^*, H. Ould Cadi, T. Sahraoui, F. Z. El Kebir

Laboratory of Biology of Development and Differentiation, Department of Biology, Faculty of Natural Science and Life, University of Oran 1-Ahmed Ben Bella, Oran, Algeria.

Treatment of cancer with chemotherapy often faces drug resistance issues, which can stop after a period of remission. This resistance is due to several mechanisms; among them, the most important is the one in relation with the overexpression of the P glycoprotein (Pgp) produced by the mdr 1 gene. This gene confers to cells the multidrug resistance (MDR) phenotype in the setting of treatment for many cancers (leukemia-lymphoma...). The aim of this study was to investigate the binding site of P glycoprotein by affinity labeling in order to synthesize effective inhibitors on chemotherapeutic drugs efflux. The first objective was to increase P glycoprotein concentration in R7 cells by treating them with doxorubicin to obtain human Pgp rich fractions. The second consisted in characterizing the progesterone binding site on Pgp by affinity photolabeling with tritiated azidopine on the one hand, and by western-blot transfer with C219 antibody on the other hand. Our results indicate a significant increase in the level of expression Pgp in R7 cells treated with 1 and 2.5 nM doxorubicin, and clearly show enrichment in Pgp of doxorubicin treated R7 cells.

P Glycoprotein, Doxorubicin, Tritiated Azidopine

Seddiki, S. , Cadi, H. , Sahraoui, T. and Kebir, F. (2018) Involvement of P Glycoprotein from Human R7 Cells Derived from Erythroleukemia in Its Attachment to the Progesterone Binding Site. Journal of Cancer Therapy, 9, 299-306. doi: 10.4236/jct.2018.93027.