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Article

Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo

1
Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany
2
Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany
3
Department of Clinical Pharmacology, Greifswald University Medical Center, 17475 Greifswald, Germany
4
General-, Visceral-, and Thoracic Surgery, Helios Clinic Schleswig, 24837 Schleswig, Germany
*
Author to whom correspondence should be addressed.
Authors contributed equally to the work as first authors.
Cancers 2020, 12(1), 123; https://doi.org/10.3390/cancers12010123
Submission received: 28 November 2019 / Revised: 19 December 2019 / Accepted: 27 December 2019 / Published: 2 January 2020
(This article belongs to the Special Issue Plasma in Cancer Treatment)

Abstract

Pancreatic cancer is one of the most aggressive tumor entities. Diffuse metastatic infiltration of vessels and the peritoneum restricts curative surgery. Standard chemotherapy protocols include the cytostatic drug gemcitabine with limited efficacy at considerable toxicity. In search of a more effective and less toxic treatment modality, we tested in human pancreatic cancer cells (MiaPaca and PaTuS) a novel combination therapy consisting of cytostatic drugs (gemcitabine or cisplatin) and gas plasma-conditioned Ringer’s lactate that acts via reactive oxygen species. A decrease in metabolic activity and viability, change in morphology, and cell cycle arrest was observed in vitro. The combination treatment was found to be additively toxic. The findings were validated utilizing an in ovo tumor model of solid pancreatic tumors growing on the chorion-allantois membrane of fertilized chicken eggs (TUM-CAM). The combination of the drugs (especially cisplatin) with the plasma-conditioned liquid significantly enhanced the anti-cancer effects, resulting in the induction of cell death, cell cycle arrest, and inhibition of cell growth with both of the cell lines tested. In conclusion, our novel combination approach may be a promising new avenue to increase the tolerability and efficacy of locally applied chemotherapeutic in diffuse metastatic peritoneal carcinomatosis of the pancreas.
Keywords: anticancer drugs; combination therapy; kINPen; plasma medicine; reactive oxygen and nitrogen species; ROS anticancer drugs; combination therapy; kINPen; plasma medicine; reactive oxygen and nitrogen species; ROS

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MDPI and ACS Style

Liedtke, K.-R.; Freund, E.; Hermes, M.; Oswald, S.; Heidecke, C.-D.; Partecke, L.-I.; Bekeschus, S. Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo. Cancers 2020, 12, 123. https://doi.org/10.3390/cancers12010123

AMA Style

Liedtke K-R, Freund E, Hermes M, Oswald S, Heidecke C-D, Partecke L-I, Bekeschus S. Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo. Cancers. 2020; 12(1):123. https://doi.org/10.3390/cancers12010123

Chicago/Turabian Style

Liedtke, Kim-Rouven, Eric Freund, Maraike Hermes, Stefan Oswald, Claus-Dieter Heidecke, Lars-Ivo Partecke, and Sander Bekeschus. 2020. "Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo" Cancers 12, no. 1: 123. https://doi.org/10.3390/cancers12010123

APA Style

Liedtke, K.-R., Freund, E., Hermes, M., Oswald, S., Heidecke, C.-D., Partecke, L.-I., & Bekeschus, S. (2020). Gas Plasma-Conditioned Ringer’s Lactate Enhances the Cytotoxic Activity of Cisplatin and Gemcitabine in Pancreatic Cancer In Vitro and In Ovo. Cancers, 12(1), 123. https://doi.org/10.3390/cancers12010123

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