ADI promoted chemosensitivity to GEM
. A, The effect of ADI and/or GEM treatment on the growth of PANC-1 tumors in BALB/c athymic mice are shown. All treatment groups resulted in significant reduction in tumor volume after 24 days relative to the control group; however, the treatment with both ADI and GEM resulted in the greatest growth inhibition overall. Further, ADI + GEM significantly inhibited tumor growth when compared to GEM alone during days 15 to day 24. *, P < 0.05, **, P < 0.01, ***, P < 0.001 as compared with vehicle group. #, P < 0.05, as compared with GEM or ADI alone group. B, Representative images of pancreatic tumors obtained from the mice treated with control, ADI, GEM, or ADI + GEM are shown. The tumors were collected at the end of the 24-day treatment period. The combined treatment of ADI + GEM resulted in the greatest reduction of tumor growth. C, Proposed model for how ADI sensitizes pancreatic cancer cells to GEM and results in cell death. ADI deprives cells of arginine which leads to inhibition of STAT and PI3K/Akt pathways. As a consequence, NF-κB activity and nuclear translocation are reduced leading to decreased synthesis of pro-survival proteins and increased synthesis of pro-death proteins. These events sensitize pancreatic cancer cells to chemotherapy (GEM) resulting in cell death.