SYNERGISTIC ANTITUMORAL EFFECT OF COMBINED GEMCITABINE WITH CATECHOL- RUTINOSIDE BY INHIBITING DCLK1 EXPRESSION IN PANCREATIC CANCER

MOLEJON, MARIA I; WEIZ, GISELA; BRECCIA JAVIER D; VACCARO, MARIA I

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

Abstract/Resumen: Doublecortin-like kinase1 (DCLK1) is upregulated in various cancers including pancreatic ductal adenocarcinoma (PDAC). Although the standard first-line treatment for pancreatic cancer is the use of gemcitabine alone, the resistance to this compound is a common cause of therapeutic failure in this type of cancer. Combined chemotherapy with a second drug constitutes an interesting strategy to inhibit malign cells and/or prevent the emergence of resistance. Owing to the difunctional benzene, catechol, has antitumor activity against many cancers while its effect on PDAC remains unknown. We explored the anti-cancer activity of an enzymatically glycosylated variant of the aromatic compound (catechol-rutinoside) combined with gemcitabine on the human pancreatic cancer cells (PANC-1). Interestedly, the addition of the glycosidic moiety, rutinose, significantly chemo-sensitized gemcitabine-resistant cells. We also evaluated the expression of DCLK1 in primary pancreatic tumoral cells, and found that DCLK1 expression y highly associated with gemcitabine resistance. Moreover, the effect of gemcitabine treatment combined with conjugated catechol exerted an interesting synergistic inhibitory effect on PDAC cells associated to the inhibition of the expression of DCLK1.