Additional file 2: Figure S2. of FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine

FRAX597 and gemcitabine decreased Ki67 staining on orthotopic pancreatic tail tumours. Pan02 murine pancreatic tumours from the orthotopic pancreatic tail tumour model treated with saline (control; CT), FRAX597 (FRAX), gemcitabine (Gem), or FRAX597 and gemcitabine (Gem + FRAX) at the doses given in the Materials and Methods section, were fixed and stained for the proliferative marker, Ki67. Three representative images were taken from each treatment group. (PPTX 2275 kb

Additional file 1: Figure S1. of FRAX597, a PAK1 inhibitor, synergistically reduces pancreatic cancer growth when combined with gemcitabine

PAK1 Knock-down (KD) effects on survival and ERK expression. PAK1 KD cells were measured in the presence (darker bars) and absence (lighter bars) of FBS to measure survival, using thymidine-withdrawal. Survival in PANC-1 PAK1 KD clones (A) was significantly lower but no difference was observed in MiaPaCa-2 PAK1 KD clones (B). No reduction in the expression of either phospho-ERK (pERK1/2) or total ERK (ERK1/2) was detected in either PANC-1 (C) or MiaPaCa-2 (D) PAK1 KD cells, as assessed by western blot. The data represent mean ± SEM, summarised from three independent experiments. *** p < 0.001, compared to the corresponding clone with FBS. (PPTX 433 kb

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