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

Abstract

<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