Glaucarubinone combined with gemcitabine improves pancreatic cancer survival in an immunocompetent orthotopic murine model

2016-12

Yeo, Dannel

Huynh, Nhi

Beutler, John A

Baldwin, Graham S

He, Hong

Nikfarjam, Mehrdad

Gemcitabine

Glaucarubinone

Prostatic Neoplasms

Journal Article

0000-0002-0944-8747

0000-0003-4866-276X

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 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. 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

link

Journal of Investigative Surgery 2016; 29(6): 366-372

Journal of Investigative Surgery