Histone deacetylases, microRNA and leptin crosstalk in pancreatic cancer

Figure 3 Leptin effects on pancreatic cancer stem cells and histone deacetylases in pancreatic cancer tumorspheres. Representative cartoon of the effects of leptin on PC cells in vitro. Leptin induced the expression of PCSC markers (CD24⁺/CD44⁺/ESA⁺, CD133⁺ and ALDH1⁺). Leptin also increased the levels of ABCB1 [P-glycoprotein 1 or multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1], which is involved in chemoresistance. Additionally, leptin induced the expression of HDAC type I (HDAC 2, 3 and 8). Leptin attenuates the cytotoxic effects of gemcitabine on PC. PC cells were cultured in low attachment plates containing mammocult media (Stem Cell Technol.), which allow the growth of tumorspheres. The tumorspheres were treated for 6 d with leptin (1.2 nmol/L), IONP-LPrA2 (a leptin antagonist bound to iron oxide nanoparticles; 0.0072 pmol/L), and gemcitabine (2 μmol/L). PC viability, PCSC markers and HDAC expression were determined by flow cytometry. Experiments were repeated three times[32,33,81,95].