Skip to main content
. 2015 Mar 16;9(4):3540–3557. doi: 10.1021/acsnano.5b00510

Figure 3.

Figure 3

Determination of GEM and GEM metabolites in PANC-1 xenografts. (A) Schematic to show the metabolism and activation of GEM in pancreatic cancer. After transport into the cells, GEM is phosphorylated by deoxycytidine kinase (dCK), leading to the formation of the active dFdCTP metabolite. Stromal and cellular CDA convert GEM to an inactive metabolite, dFdU. CDA leads to GEM inactivation at the tumor site, implying that interference in CDA expression could prolong GEM pharmacokinetics, leading to increased drug uptake at the tumor site. (B) HPLC and quantification of total GEM and GEM metabolite (dFdU and dFdCTP) concentrations in the tumor tissue. The HPLC experiment was carried out in a separate batch of animals that were IV injected with the same amounts free GEM, GEM LB-MSNP, and PTX/GEM LB-MSNP as described in Figure 2A; *p < 0.05 compared with free GEM, #p < 0.05 compared with GEM plus 1× dose Abraxane.