Irreversible electroporation (IRE) can be used to treat cancer by electrical pulses, with advantages over traditional thermal approaches. Here we assess for the first time the IRE response of pancreatic cancer, one of the deadliest forms of cancer, both in vitro and in vivo. We demonstrate that both established and primary cancer cell lines can be destroyed by IRE, but with differential susceptibility and thresholds. We further demonstrate in vitro that viability for a given IRE dose can vary with the local chemistry as outcomes were shown to depend on suspending medium and reduction of glucose in the media significantly improved IRE destruction. Data here also demonstrate that repeated IRE treatments can lead to adaptive resistance in pancreatic carcinoma cells thereby reducing subsequent treatment efficacy. In addition, we demonstrate that physical enhancement of IRE, by re-arranging the pulse sequences without increasing the electrical energy delivered, achieve reduced viability in vitro and decreased tumor growth in an in vivo xenograft model. Together, these results show that IRE can destroy pancreatic cancer in vitro and in vivo, that there are both chemical and physical enhancements that can improve tumor destruction, and that one should guard against adaptive resistance when performing repeated treatments.
Bibliographical noteFunding Information:
This study was supported by Boston Scientific and the University of Minnesota Institute for Engineering in Medicine (IEM) Cancer Animal Core. QS was partially supported by Doctoral Dissertation Fellowship, University of Minnesota. JB was supported by the Carl and Janet Kuhrmeyer Chair in the Department of Mechanical Engineering. PPP was supported by the NIH (R01CA181385 and U54CA210190) and the Randy Shaver Research and Community Fund. KEG was supported by the CSE Fellowship and the ARCS Foundation. The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funding agencies. We thank Marjorie Carlson for assistance with the KPC mouse models. We also thank Navid Manuchehrabadi, Hong Cao, Kanav Khosla and Tim Ostroot for helpful discussions and technical support.
© 2017, Biomedical Engineering Society.
Copyright 2018 Elsevier B.V., All rights reserved.
- Cancer treatment
- In vitro
- In vivo
- Irreversible electroporation
- Pancreatic cancer