Figure 7.

FTY720 in combination with gemcitabine inhibited the tumor progression and desmoplasia in a syngeneic model of pancreatic cancer. (A) Representative bioluminescent images of the C57Bl/6 mouse implanted with PAN 02-luc (5×10⁴ cells). (B) The tumor volumes in mice measured on last day expressed in cm³. (C) The paraffin embedded sections were stained with hematoxylin and eosin and representative H&E images of each group. (D) Representative images of tissue sections of α-SMA staining (left panel). (E) Representative images of tissue sections of Sirius red staining (right panel).Statistical analysis was performed using one way ANOVA followed by post hoc Tukey test; * p≤0.001 vs control. (F) Graphic illustration of mode of action of FTY720 in combination with gemcitabine in pancreatic cancer. FTY720 reduces the cell proliferation by decreasing the expression of certain proliferation markers and by activation of PP2A (red star). It also abrogates HIF1α/CXCL12/CXCL4 loop, Shh pathway resulting in reduced desmoplasia and metastasis. This reduction in desmoplastic content leads to increased accumulation of gemcitabine and thereby increased sensitivity through altering gemcitabine metabolizing genes.