Feasibility and Safety of Electrochemotherapy (ECT) in the pancreas: a pre-clinical investigation.
Background. Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that is generally refractory to standard chemotherapeutic agents; therefore, improvements in anticancer therapies are warranted. Poor drug delivery to neoplastic cells due to an extensive stromal reaction is one of the major determinant of therapeutic resistance in PDAC. Electroporation (EP) can be used in vivo to increase the local uptake of chemotherapeutic agents by cancer cells (electrochemotherapy, ECT), thus leading to enhanced tumour response rate. In the present study, we evaluated the in vivo effects of reversible electroporation to normal pancreas using an experimental model of rabbit. In parallel, we also tested the effect of electroporation in increasing the sensitivity to chemotherapeutic of pancreatic cancer cell lines. .Materials and methods. The application in vivo of the ESOPE standard pulse protocol (1000 V/cm, 8 pulses, 100 µs, 5 KHz) to normal rabbit pancreas was tested in New Zealand White Rabbits and short and long-term toxicity assessed. PANC1 and MiaPaCa2 cell lines were tested for in vitro electrochemotherapy experiments. Cell permeabilization levels were determined by flow cytometry whereas cell viability and drug sensitivity of pulsed cells to cisplatin and bleomycin were measured by trypan-blue exclusion method. Results. In healthy rabbit, neither systemic nor local toxic effects due to the EP procedure were observed, this demonstrating the safety of the optimized electric parameters for the treatment to pancreas in vivo. In parallel, we established an optimized protocol for ECT in vitro where the effect of bleomycin and cisplatin where enhanced with respect to treatment without ECT.