Figure 5.
Suppression of the PARP1-HMGB1 pathway increases sensitivity to TNFSF10 in vivo. (A) Pancreatic tumor cells with PARP1 and HMGB1 knockdown are more sensitive to TNFSF10 in vivo. SCID mice were injected subcutaneously with indicated human pancreas cancer PANC-1 cells (2 × 106 cells/mouse) and treated with TNFSF10 (10 mg/kg/ i.v. twice daily) at d 7 for 2 wk. Tumor volume was calculated weekly. Data represent mean ± SE (n = 5 to 8 mice/group, * P < 0.05). (B) Western blot analysis of the indicated protein expression in isolated tumor at d 28 in TNFSF10 treatment group. (C) Autophagy was assayed by MAP1LC3A staining and apoptosis was assayed by TUNEL staining in isolated tumor atd 28. Yellow arrows show MAP1LC3A punctate and TUNEL positive cells, respectively. Quantifications of MAP1LC3A- and TUNEL-positive tumor cells were performed in the tumor sections (n=5 mice/group, * P < 0.05 versus control shRNA group; bar: 30 μm).