Palbociclib suppresses the cancer stem cell properties and cell proliferation through increased levels of miR-506 or miR-150 in Panc-1 and MiaPaCa-2 cells

The prognostic characteristics of pancreatic cancer (PC) are determined by the contributing factors from tumor microenvironment. Leptin is a critical oncogenic factor released adipocytes as an adipokine into microenvironment, where it promotes development activating stem cell (CSC) molecular regulators Notch, Hedgehog, and Wnt/ß-catenin signaling. One downstream targets these pathways CDK4/6 cyclin D which controlled P16 INK4A that highly mutated in PC. Therefore, purpose this study was to determine effect inhibitor, palbociclib, on Leptin-induced PC cells target signaling via miR-150, miR-506, miR-208 modulation. treatment increased ability Panc-1, MiaPaCa-2, Capan-2 proliferate decreased palbociclib. Additionally, tumorspheres were generated Leptin-treated (Leptin+) Leptin-untreated (Leptin-) Panc-1 MiaPaCa-2 transfected with miR-150 (tumorsuppressor miRNAs), or anti-miR-208 (oncomiR), followed palbociclib treatment. Forced expression miR-506 significantly susceptibility Leptin+ inhibiting colony spheroid formation, CD44 cells. more effective at N-cadherin, ß-catenin, p-GSK3ß, Wnt5a/b Leptin-/+ As result, suppressed CSC profile induced leptin treatment, both tumorsphere forms leptin-targeted pathways, thereby disabling cells' resistance mechanism. Increased inhibition enhanced sensitivity proved combining inhibitors improves success rate proliferation.