40 The Effect of Gemcitabine on the Release of Microparticles and Cytokines in Pancreatic Cancer

Abstract Aim Pancreatic cancer (PC) has poor survival outcomes due to late diagnosis and use of somewhat ineffective gemcitabine chemotherapy. Phosphatidylserine (PS) and tissue factor (TF) expressing microparticles are increased at late-stage PC and associated with venous thromboembolism. Basigin expressing microparticles and pro-inflammatory cytokines facilitate metastasis and disease progression. This study aims to determine the effects of gemcitabine on the inflammatory status of PC at early (EDS) and late (LDS) disease stages. Method PC cell line PANC-1 were incubated with recombinant human TF to model EDS and LDS PC, both with and without gemcitabine chemotherapy treatment in vitro. Flow cytometry was performed on the supernatants to identify PS+, TF+ and basigin+ microparticles using fluorochrome-labelled antibodies. ELISAs were performed on the culture supernatants to quantify concentrations of IL-4, IL-6, CXCL12 and TNF-α. Results The number of microparticles released, and their expression of PS, TF or basigin, did not change upon disease progression nor in the presence of gemcitabine. The levels of IL-4 in EDS were significantly lower than in LDS in the presence of gemcitabine (P<0.03). The presence of gemcitabine reduced the release of both IL-6 and CXCL12 in both EDS and LDS, but not significantly. Conclusions Further research on microparticles and cytokines is needed to fully understand their effect on PC disease progression and treatment efficacy. IL-4 might represent a potential pharmacological target to mitigate inflammation-induced metastasis in PC.