The role of P-glycoprotein and breast cancer

24 Background and aims. Active efflux proteins such as P-glycoprotein (P-gp) are 25 thought to have a protective role in the intestinal tract by preventing xenotoxin 26 absorption. Some bacteria also need to adhere to the intestinal tract before causing 27 disease through adhesion secretion. Thus, this study was initiated to examine 28 whether any association exists between bacterial adhesion and P-gp expression. 29 Methods. Three human cell lines (Caco2, RKO, MCF7), and 6 species of bacteria 30 were used in this study (Escherichia coli, Staphylococcus aureus, Salmonella 31 typhimurium, Klebsiella pneumoniae, Clostridium sporogenes and Pseudomonas 32 aeruginosa). Following incubation of our cells with active efflux inhibitors, bacteria 33 incubated with a stable fluorescent dye were co-incubated at 37°C for various times 34 up to 240 min. Fluorescence intensity was used to compare bacterial attachment to 35 these cell lines with either normal efflux protein expression or with induction or 36 inhibition of efflux proteins. Results. P-gp inhibition by either PSC-833 or GF120918 37 resulted in a significant increase of all bacterial attachment to Caco2 cells upto 3 fold. 38 RKO cells and MCF7 cells did not alter their bacterial attachment with PSC-833. 39 Fumitremorgen C, a dedicated BCRP inhibitor had no effect. In addition, rifampicin, a 40 P-gp inducer, resulted in some limited reduction in Salmonella and Klebsiella 41 attachment only. Conclusions. These results indicate P-gp expression may 42 contribute to the resistance of potential bacterial toxicity, by preventing them 43 adhering to human enterocytes cells in the gastrointestinal tract, which may reduce 44 the risk or intensity of gastrointestinal disorders. 45 46 47