Abstract
Despite the rapid progression of cancer pharmacotherapy, the high drug resistance of pancreatic ductal adenocarcinoma (PDA) makes it one of the most lethal malignancies. Therefore, there are high expectations associated with experimental therapies, such as electrochemotherapy (ECT). This technique involves the application of short electric pulses to induce transitional permeabilization of the cellular membrane, thus enhancing drug molecules influx. The aim of the study was to investigate the influence of electroporation with cisplatin (CisEP) on the primary culture of human PDA cells from lung metastases—their survival and stress response. Considering the growing importance of various research models, two established human PDA cell lines, EPP85-181P (sensitive to daunorubicin) and EPP85-181RDB (resistant to daunorubicin), were utilized as a reference control. Cisplatin revealed higher cytotoxicity towards established cell lines. Following CisEP application, we observed a significant decrease of cells viability in the primary culture model. After CisEP therapy, an increased immunoreactivity with SOD-2 and Casp-3 antibodies was noticed. In conclusion, we discovered that electroporation can enhance the cytotoxic effect of cisplatin in pancreatic cancer cells in vitro. This effect was evident for cells from the primary culture. The obtained results confirm the importance of primary cells models in studies on the efficacy of experimental cancer therapies.
Highlights
Worldwide, over 200,000 people are diagnosed with pancreatic cancer every year
The distinguishing between pulmonary adenocarcinoma and fibroblasts was made according to literature [20] and the diagnostic procedures applied in clinical unit from where the tissue sections were collected; we examined the immunoreactivity of thyroid transcription factor 1 (TTF-1) mouse monoclonal antibody (Life Technologies, cat. no. 80221) in dilution 1 : 50, cytokeratin 7 (CK 7) mouse monoclonal antibody
In the experiment conducted by Girelli group (2015) similar effect was observed on PANC1 cell line where cisplatin IC50 was decreased from 23 μM to 8 μM following the application of electric pulses
Summary
Over 200,000 people are diagnosed with pancreatic cancer every year. The highest risk of morbidity (approximately 8–12/105 males and 6-7/105 women) relates to the population of industrialized countries, where pancreatic cancer is the fifth most common cause of cancer-related mortality. In the United States, malignant tumors of the pancreas are currently one of the four leading causes of cancer-related death and are expected to become the second within the two decades [1]. Such high mortality rates result from late diagnosis and extremely aggressive character of the neoplasm. Among methods supporting the transport of chemotherapeutic agents into cells, the electroporation (EP) seems to be promising The basis of this technique is exposing the cell to the pulsed electric field action which can cause a dual effect:
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