Page 70 - SDIR5 Abstract book 21 12 2021.
P. 70

POSTER PRESENTATIONS



               P30



                       I1-imidazoline receptor ligand inhibits P-glycoprotein efflux in pancreatic ductal
                                                   adenocarcinoma cells

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                       Marija Ostojić , Tatjana Srdić-Rajić , Marijana Pavlović , Kristina Živić , Jelena Grahovac
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                 1 Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, 11000 Belgrade, Serbia

               Background: One of the most common causes of treatment failure in cancer is overexpression of drug efflux
               pumps,  which  leads  to  decreased  intracellular  drug  accumulation  and  chemotherapy  efficacy.  P-
               glycoprotein (P-gp) is one of the most studied membrane drug efflux transporters, frequently expressed in
               pancreatic ductal adenocarcinoma (PDAC) and contributing to its poor 5-year survival rate of just 6%. The
               aim of this study was to examine the effects of I1-imidazoline receptor ligands clonidine, moxonidine,
               rilmenidine, and efaroxan on the P-gp levels and function in PDAC cells in vitro. These drugs contain an
               imidazoline  ring  within  their  structure  that  may  inhibit  the  activity  of  adenosine  triphosphate  (ATP)  -
               sensitive channels, such is P-gp. Material and Methods: The effect of tested compounds on Calcein AM
               efflux  was  examined  using  flow  cytometry  for  adherent  Panc-1  and  MiaPaCa-2  cells,  and  fluorescent
               microscopy for same cells grown in 3D culture. P-gp surface levels in PDAC cells were analyzed by flow
               cytometry after 48h of treatment with 100µM rilmenidine. Results: Out of the tested compounds, only
               rilmenidine inhibited Calcein AM efflux, and it did so in a dose dependent manner in both 2D and 3D
               cultures.  Importantly,  treatment  with  100µM  rilmenidine  did  not  have  significant  effects  on  the  P-gp
               expression in PDAC cells. Conclusion: Our preliminary findings indicate that rilmenidine has a potential to
               help overcome multidrug resistance in PDAC. Given that rilmenidine can target several other aspects of the
               PDAC  pathology  (cell  invasiveness,  survival,  metabolism,  and  the  microenvironment),  it  holds  a  great
               promise for developing more effective PDAC treatment.
               Keywords: pancreatic ductal adenocarcinoma, P-glycoprotein, rilmenidine
















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