we demonstrate that N threo 1 phenyl 2 decanoylamino 3 morpholino 1 propanol, a glucosylceramide synthase inhibitor and gemcitabine, a nucleoside analog, improve the antitumor activity of Lip C6. We Lenalidomide solubility show that the biological impact of Lip C6 is achieved through inhibition of Akt phosphorylation, and suggest that the distinctive action of the anti metabolite gemcitabine may be used to prime the PANC 1 cells to the action of Lip C6. Additionally, using a nanoliposomal mix of C6 and PDMP ceramide, we demonstrate that the inhibition of glucosylceramide synthase helps the anti pancreatic cancer activity of C6 ceramide. Altogether this study illustrates the application of combinatorial C6 ceramide containing nanotherapeutics as a possible new strategy in treating drug-resistant human pancreatic cancer. Lip C6 cytotoxicity is synergistically increased by gemcitabine or Lip PDMP. We’ve previously noted that Lip C6 induces cytotoxicity in many different cancer cell lines. In this study, we evaluated the power of Lip C6, gemcitabine and Lip PDMP, to trigger cell death of PANC 1 pancreatic Metastatic carcinoma cancer cells. Gemcitabine is a FDA approved chemotherapeutic that’s typically used in the treatment of pancreatic cancer. We formulated Lip PDMP being a formulation designed to stop the neutralization of ceramide to glucosylceramide. In this review, we hypothesized that gemcitabine or Lip PDMP could increase the efficacy of Lip C6. In time and amount assessments of cellular viability, the IC50 in PANC 1 cells for Lip C6 and Lip PDMP at 48 h was decided to be about 26 and 48 uM, respectively. On the other hand, the IC50 for gemcitabine in PANC 1 cells was extrapolated to be substantially more than 1,000 uM. This statement was consistent with previously published observations that suggested PANC 1 cells were very resistant to gemcitabine. 30 Lip C6, gemcitabine EMD?121974 and Lip PDMP were considered in combination using the Chou Talalay approach to measure potential synergistic cell-killing. The mix list for different levels of Lip C6 and gemcitabine revealed that these anticancer agents acted in synergy with one another. But, the CI for different concentrations of Lip PDMP and Lip C6, or Lip PDMP and gemcitabine, unveiled these agents could synergize with or antagonize one another. The normal agent to these contradictory results was Lip PDMP, a regulator of sphingolipid k-calorie burning that potentially could influence a variety of pro survival or pro apoptotic sphingolipids. We next employed the method to determine if mixtures of Lip C6, gemcitabine or Lip PDMP, at concentration that were not individually detrimental to cellular viability, could induce apoptosis of PANC 1 cells. No effect was seen with 5 uM Lip C6 alone, 20 uM gemcitabine alone or Lip PDMP 5 uM alone.