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

ROS anticancer drugs combination therapy kINPen plasma medicine reactive oxygen and nitrogen species

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
02 Jan 2020
Historique:
received: 28 11 2019
revised: 19 12 2019
accepted: 27 12 2019
entrez: 8 1 2020
pubmed: 8 1 2020
medline: 8 1 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 31906595
pii: cancers12010123
doi: 10.3390/cancers12010123
pmc: PMC7017174
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : Bundesministerium für Bildung und Forschung
ID : 03Z22DN11

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Kim-Rouven Liedtke (KR)

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.

Eric Freund (E)

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.
Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany.

Maraike Hermes (M)

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.
Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany.

Stefan Oswald (S)

Department of Clinical Pharmacology, Greifswald University Medical Center, 17475 Greifswald, Germany.

Claus-Dieter Heidecke (CD)

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.

Lars-Ivo Partecke (LI)

Department of General, Visceral, Thoracic and Vascular Surgery, Greifswald University Medical Center, 17475 Greifswald, Germany.
General-, Visceral-, and Thoracic Surgery, Helios Clinic Schleswig, 24837 Schleswig, Germany.

Sander Bekeschus (S)

Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology (INP Greifswald), 17489 Greifswald, Germany.

Classifications MeSH