HDAC inhibitors induce anti tumor effect of IL-13Rα2 targeted immmunotoxin IL13-PE in IL-13Rα2-negative pancreatic cancer cell lines. A, Cytotoxicity assay was performed in IL-13Rα2-negative and -positive pancreatic cancer and normal cell lines. Cells were pre-treated with 0 - 5 μM TSA for 24 hours and then treated with 0 - 1000 ng/ml IL-13-PE for 20 hours in leucine-free medium. Protein synthesis was evaluated by H3-leucine incorporation. Percentage cytotoxicity was calculated with no treatment control as 100%. B and C, Regression of IL-13Rα2-negative pancreatic tumors (Panc-1 and ASPC-1) treated with 5 mg/kg TSA and/or 100 μg/kg IL-13-PE as described in methods. Mock combination means tumors were mock transected with control vector and treated with HDAC inhibitors and IL-13-PE in vivo. D and E, Regression of IL-13Rα2-negative pancreatic tumors treated with SAHA and/or IL-13-PE. Mice were treated daily with i.p. injection of SAHA (25 mg/kg) from day 4 after tumor implantation for two weeks followed by i.t. injection of IL-13-PE (100 μg/kg) from day 5 for two weeks. F and G, Regression of IL-13Rα2-posotive pancreatic tumors (HS766T and MIA-PaCa2) treated with SAHA and/or IL-13-PE. The schedule of treatment was similar as in panel D and E. Statistical significances are shown by *: P < 0.05, †: P < 0.001.