Effects of the high-affinity Peptide reversin 121 on multidrug resistance proteins in experimental pancreatic cancer.
OBJECTIVE
Multidrug resistance (MDR) is the major obstacle in the treatment of pancreatic carcinoma. Recent studies indicate resistance-modulating effects of high-affinity peptides.


METHODS
Pancreatic cancer was induced in an ultrasound-guided orthotopic mouse model. Expression and function of MDR proteins (MRPs) P-glycoprotein MRP1 and MRP3 were analyzed in vitroandin vivo by multicolor flow-cytometric analysis. Proliferation of tumor cells was evaluated with a nonradioactive proliferation assay. Animals and cells received standard chemotherapy or chemotherapy plus the high-affinity peptide reversin 121 (R121).


RESULTS
The proportions of P-glycoprotein-, MRP1- and MRP3-positive tumor cells increased significantly after chemotherapy in vitro and in vivo. Drug efflux activity increased after chemotherapy. Addition of R121 to chemotherapeutic regimens significantly reduced the proportions of tumor cells positive for MRPs in vitroandin vivo. Tumor size and prevalence of metastases decreased significantly compared to untreated controls.


CONCLUSIONS
Beneficial effects of high-affinity peptide R121 on reversing chemotherapy-induced MDR were demonstrated in pancreatic cancer.
Hoffmann
Katrin
K
Department of General Surgery, Ruprecht-Karl University, Heidelberg, Germany. katrin.hoffmann@med.uni-heidelberg.de
Bekeredjian
Raffi
R
Schmidt
Jan
J
Büchler
Markus W
MW
Märten
Angela
A
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
D018435:ATP Binding Cassette Transporter, Subfamily B; D009842:Oligopeptides; C120260:reversin 121