Glaucarubinone Combined with Gemcitabine Improves Pancreatic Cancer Survival in an Immunocompetent Orthotopic Murine Model

<p><i>Background</i>: Pancreatic cancer continues to have a poor survival rate with an urgent need for improved treatments. Glaucarubinone, a natural product first isolated from the seeds of the tree <i>Simarouba glauca</i>, has recently been recognized as having anti-cancer properties that may be particularly applicable to pancreatic cancer. <i>Methods</i>: The effect of glaucarubinone on the growth and migration of murine pancreatic cancer cells was assessed by ³H-thymidine incorporation assay. The survival impact of glaucarubinone alone and in combination with gemcitabine chemotherapy was assessed using an immunocompetent orthotopic murine model of pancreatic cancer. <i>Results</i>: Glaucarubinone inhibited the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment with either glaucarubinone or gemcitabine reduced proliferation <i>in vitro</i> and the combination was synergistic. The combination treatment improved survival two-fold compared to gemcitabine treatment alone (<i>p</i> = 0.046) in PAN02 cells. <i>Conclusions</i>: The synergistic inhibition by glaucarubinone and gemcitabine observed <i>in vitro</i> and the improved survival <i>in vivo</i> suggest that glaucarubinone may be a useful adjunct to current chemotherapy regimens.</p

Additional file 1: Figure S1. of Depletion of p21-activated kinase 1 up-regulates the immune system of APC∆14/+ mice and inhibits intestinal tumorigenesis

PF-3758309 increased the numbers of white blood cells, and splenic weight and white pulp area, in SCID mice. HCT116 human CRC cells were grown as xenografted tumours in SCID mice for 2 weeks. The mice (n = 6) were then treated with PF-3758309 by peritoneal injection (25 mg/Kg) for a further 2 weeks. The mice were then culled, the blood taken for blood cell count and the spleens weighed, fixed in formalin, sectioned and stained with H&E. Control mice (n = 4) were treated with 5% DMSO in saline. Cont: control; WCC: white blood cell; neut: neutrophil; lym: lymphocyte; mono: monocytes. *, p < 0.05, **, p < 0.01, compared to control (PPTX 566 kb