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

J Invest Surg 2016 Dec 30;29(6):366-372. Epub 2016 Mar 30.

a Department of Surgery , University of Melbourne, Austin Health , Melbourne , Victoria , Australia.

Background: 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 Simarouba glauca, has recently been recognized as having anti-cancer properties that may be particularly applicable to pancreatic cancer.

Methods: The effect of glaucarubinone on the growth and migration of murine pancreatic cancer cells was assessed by H-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.

Results: Glaucarubinone inhibited the growth of the murine pancreatic cancer cell lines LM-P and PAN02. Treatment with either glaucarubinone or gemcitabine reduced proliferation in vitro and the combination was synergistic. The combination treatment improved survival two-fold compared to gemcitabine treatment alone (p = 0.046) in PAN02 cells.

Conclusions: The synergistic inhibition by glaucarubinone and gemcitabine observed in vitro and the improved survival in vivo suggest that glaucarubinone may be a useful adjunct to current chemotherapy regimens.

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