5th World Congress on Cancer Therapy
University of Pisa, Italy
Introduction: Current therapy for PDAC is surgery followed by adjuvant chemotherapy for early-stage and palliative chemotherapy for advanced disease. Gemcitabine is the standard drug in both adjuvant and palliative treatment. Th e mixture of Alkaloids (NSC-631570) in combination with gemcitabine signifi cantly increased the median survival of advanced PDAC patients with respect to gemcitabine alone (10.4 vs 5.2 months; p<0.001). Furthermore, preclinical studies showed that this mixture had selective citotoxic eff ects in cancer cell lines derived from diff erent tumor types, but not in normal cell lines. Aim: To evaluate the citotoxic eff ects of NSC-631570 in 2 Primary Pancreatic Cancer Cell Lines (PPTCCs), fi broblasts derived from PDAC specimens (F-PDAC) and an immortalized epithelial ductal pancreatic cell line (HNPE). Materials & Methods: Cytotoxicity was assessed by the CellTiter 96 kit (Promega) based on the cellular metabolism of the tetrazolium compound XTT, which is reduced by living cells to yield a soluble formazan product in the presence of the electron coupling agent phenazine methosulfate, while the modulation of Ukrain uptake in the medium was studied using the fl uorescence property of NSC-631570 with the AlphaDigiDoc soft ware by UV light excitation (ULA-DC test). Results: Citotoxic eff ects of Ukrain in PPTCCs were signifi cantly higher than those observed in F-PDAC and HPNE cells (20% vs. 80% alive cells, at 10 μM [drug]). Furthermore, the ULA-DC test revealed that PPTCCs cells consumed more drug than F-PDAC and HPNE cells (paired Student’s test, n=4, p<0.001). Conclusion: Th ese data demonstrated the selective eff ect of NSC-631570 in PPTCCs, which may be related to a diff erent transport system or higher metabolism of the drug in PDAC. Indeed, the two diff erents up-take of alkaloids discovered in cancer and non cancer pancreatic cells seem to suggest an higher expression of multi drug resistant systems (MDR) in F-PDAC and HPNE cells and warrant further investigations in order to support the possible role of Ukrain in PDAC treatment.