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Article

Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma

1
Institut national de la santé et de la recherche médicale (Inserm), Centre de recherche Saint-Antoine, CRSA, Sorbonne Université, 75012 Paris, France
2
LPP (Laboratoire de physique des plasmas, UMR 7648), Sorbonne Université, Centre national de la recherche scientifique (CNRS), Ecole Polytechnique, 75005 Paris, France
3
TGF-β and Cancer Group, Oncobell Program, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Barcelona, Spain
4
Oncology Program, CIBEREHD, National Biomedical Research Institute on Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III, 28029 Madrid, Spain
5
Inserm, Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université, 75013 Paris, France
6
Department of Hepatobiliary Surgery and Liver Transplantation, Pitié-Salpêtrière Hospital, Assistance publique-Hôpitaux de Paris (AP-HP), 75013 Paris, France
7
Department of Hepatology, Reference Center for Inflammatory Biliary Diseases and Autoimmune Hepatitis (Centre de référence maladies rares (CRMR), maladies inflammatoires des voies biliaires et hépatites auto-immunes (MIVB-H), AP-HP, 75012 Paris, France
*
Authors to whom correspondence should be addressed.
Co-senior authors.
Cancers 2020, 12(5), 1280; https://doi.org/10.3390/cancers12051280
Received: 23 April 2020 / Accepted: 15 May 2020 / Published: 19 May 2020
(This article belongs to the Special Issue Plasma in Cancer Treatment)
Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA in both an in vivo and in vitro context. In vivo, using subcutaneous xenografts into immunocompromised mice, CAP treatment of CCA induced DNA lesions and tumor cell apoptosis, as evaluated by 8-oxoguanine and cleaved caspase-3 immunohistochemistry, respectively. The analysis of the tumor microenvironment showed changes in markers related to macrophage polarization. In vitro, the incubation of CCA cells with CAP-treated culture media (i.e., plasma-activated media, PAM) led to a dose response decrease in cell survival. At molecular level, CAP treatment induced double-strand DNA breaks, followed by an increased phosphorylation and activation of the cell cycle master regulators CHK1 and p53, leading to cell cycle arrest and cell death by apoptosis. In conclusion, CAP is a novel therapeutic option to consider for CCA in the future. View Full-Text
Keywords: cholangiocarcinoma; cold plasma; innovative therapy; tumor cells; macrophages; plasma selectivity; plasma jet cholangiocarcinoma; cold plasma; innovative therapy; tumor cells; macrophages; plasma selectivity; plasma jet
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MDPI and ACS Style

Vaquero, J.; Judée, F.; Vallette, M.; Decauchy, H.; Arbelaiz, A.; Aoudjehane, L.; Scatton, O.; Gonzalez-Sanchez, E.; Merabtene, F.; Augustin, J.; Housset, C.; Dufour, T.; Fouassier, L. Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma. Cancers 2020, 12, 1280. https://doi.org/10.3390/cancers12051280

AMA Style

Vaquero J, Judée F, Vallette M, Decauchy H, Arbelaiz A, Aoudjehane L, Scatton O, Gonzalez-Sanchez E, Merabtene F, Augustin J, Housset C, Dufour T, Fouassier L. Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma. Cancers. 2020; 12(5):1280. https://doi.org/10.3390/cancers12051280

Chicago/Turabian Style

Vaquero, Javier, Florian Judée, Marie Vallette, Henri Decauchy, Ander Arbelaiz, Lynda Aoudjehane, Olivier Scatton, Ester Gonzalez-Sanchez, Fatiha Merabtene, Jérémy Augustin, Chantal Housset, Thierry Dufour, and Laura Fouassier. 2020. "Cold-Atmospheric Plasma Induces Tumor Cell Death in Preclinical In Vivo and In Vitro Models of Human Cholangiocarcinoma" Cancers 12, no. 5: 1280. https://doi.org/10.3390/cancers12051280

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