Elucidation of the roles of Pim-1 induced under hypoxia in pancreatic cancer and its application to the cancer therapy

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In this study, we examined whether the inhibition of Pim-1 activity, is effective treatment pancreatic cancer, based on the findings that Pim-1 protein expression enhanced under hypoxic conditions. According to the previous reports demonstrating that the protein fused to polypeptides composed of eleven arginine can pass through the cytoplasmic membrane, we constructed an expression vector encoding 11 arginine-signal sequence of Thrombopoietin-dominant negative Pim-1 protein. PCI-43. cells, a pancreatic cancer cell line, were inoculated subcutaneously into the back of SCID mice. Then the mice were treated with the injection of the vectors into the femoral muscle. At 21 days after the treatment, the tumors in the mice treated with the injection of dominant negative PIM-1 expression vector disappeared, whereas the tumors in those treated with empty vector grew. These results suggest that the gene therapy using dominant negative Pim-1 expression vector may be effective for the cancer. However, the doses of expression vector to inject should be reduced for clinical trials. We sought small chemical compound library for the chemical compounds which could suppress the function of Pim-1. We found fourteen small chemical compounds which suppressed the phosphorylation activity of PIM-1 by more than 40 %. We are now planning to examine the in vivo anti-tumor effects of those compounds.