VEGA 2/0028/15

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Changes of leukemia cells drug sensitivity induced by changes of membrane drug transporters expression profile       

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Principal investigator: Albert Breier

Duration: January 2015 – December 2018

Coordinating institution: Institute of Molecular Physiology and Genetics, SAS, Bratislava

Annotation:

Multidrug resistance (MDR) of neoplastic cells represents real obstacle in chemotherapy of cancer diseases. Expression of P-glycoprotein (P-gp), a plasma membrane drug transporter represents most often occurred molecular cause of MDR. Several cell processes and regulatory pathways including protein glycosylation and phosphorylation are involved in P-gp mediated MDR development. Study of multi-player cellular mechanisms that may alter regulation of P-gp expression, degradation and transport activity represents highly important topic for intensive research activity. This research has potential to bring data applicable for enlargement of targeted therapeutic protocols effective for concrete type of neoplastic disease of respective individuals with multidrug resistance mediated by P-gp. The project will be focused on hematological malignancies predominantly on leukemia using different human and animal cell models.

Publications:
PubMed Messingerova L, Imrichova D, Coculova M, Zelina M, Pavlikova L, Kavcova H, Seres M, Bohacova V, Lakatos B, Sulova Z, Breier A: Different Mechanisms of Drug Resistance in Myelodysplastic Syndromes and Acute Myeloid Leukemia. (Chapter 7), In Myelodysplastic Syndromes (Ota Fuchs Ed.), InTech, ISBN 978-953-51-2586-0, 2016, pp 181-200
PubMed Pavlikova L, Seres M, Imrichova D, Hano M, Rusnak A, Zamorova M, Katrlik J, Breier A, Sulova Z. The expression of P-gp in leukemia cells is associated with cross-resistance to protein N-glycosylation inhibitor tunicamycin. Gen Physiol Biophys. 35 (2016) 497-510
PubMed Coculova M, Imrichova D, Seres M, Messingerova L, Bohacova V, Sulova Z., Breier A. The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein. Leuk Res. 36 (2016) 32-39.
PubMed Messingerova L, Imrichova D, Kavcova H, Seres M, Sulova Z., Breier A. A decrease in cellular microRNA-27a content is involved in azacytidine-induced P-glycoprotein expression in SKM-1 cells. Toxicol In Vitro. 36 (2016) 81-88.
PubMed Imrichova D, Messingerova L, Seres M, Kavcova H, Pavlikova L, Coculova M, Breier A, Sulova Z. Selection of resistant acute myeloid leukemia SKM-1 and MOLM-13 cells by vincristine-, mitoxantrone- and lenalidomide-induced upregulation of P-glycoprotein activity and downregulation of CD33 cell surface exposure. Eur J Pharm Sci. 77 (2015):29-39.
PubMed Messingerova L, Jonasova A, Barancik M, Polekova L, Seres M, Gibalova L, Breier A, Sulova Z. Lenalidomide treatment induced the normalization of marker protein levels in blood plasma of patients with 5q-myelodysplastic syndrome. Gen Physiol Biophys. 34 (2015) 399–406
PubMed Turakova K, Pavlikova L, Messingerova L, Lakatos B, Breier A, Sulova Z. Reduced udp-glucose levels are associated with p-glycoprotein over-expression in l1210 cells and limit glucosylceramide synthase activity Anticancer Research 35 (2015) 2627-2634