Page 70 - SDIR5 Abstract book 21 12 2021.
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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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