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Article

Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma

1
National Center of Rare Diseases-Cutaneous Lymphoma—Member of EuroBloodNet, Second Department of Dermatology and Venereal Diseases, Attikon University General Hospital, National and Kapodistrian University of Athens, 124 62 Athens, Greece
2
Department of Biological Chemistry, Medical School of Athens, National and Kapodistrian University of Athens, 115 27 Athens, Greece
3
Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de Cantabria, 39011 Santander, Spain
4
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III, 28029 Madrid, Spain
5
2nd Department of Internal Medicine—Propaedeutic and Research Unit, National and Kapodistrian University of Athens, Medical School of Athens, University General Hospital Attikon, 124 62 Athens, Greece
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Matthias Goebeler and Marion Wobser
Cancers 2022, 14(4), 1070; https://doi.org/10.3390/cancers14041070
Received: 25 January 2022 / Revised: 13 February 2022 / Accepted: 16 February 2022 / Published: 20 February 2022
(This article belongs to the Special Issue Cutaneous Lymphomas)
The combination of Resminostat (HDACi) and Ruxolitinib (JAKi) exerted cytotoxic effects and inhibited proliferation of CTCL cell lines (MyLa, SeAx) in vitro. The aim of the present study was to validate their antitumor effects in vivo using the chick embryo chorioallantoic membrane (CAM) model, which allows quick and efficient monitoring of tumor growth, migration, invasion, and metastatic potential. The drug combination exhibited a significant inhibition of primary tumor size, and inhibited intravasation and extravasation of tumor cells to the liver and lung. It also exerted an inhibitory effect in the migration and invasion of tumor cells and significantly reduced key signaling pathway activation. Our data demonstrate that the CAM assay could be employed as a preclinical in vivo model in CTCL for pharmacological testing, and that the combination of Resminostat and Ruxolitinib exerts significant antitumor effects in CTCL progression that need to be further evaluated in a clinical setting.
The combination of Resminostat (HDACi) and Ruxolitinib (JAKi) exerted cytotoxic effects and inhibited proliferation of CTCL cell lines (MyLa, SeAx) in previously published work. A xenograft tumor formation was produced by implanting the MyLa or SeAx cells on top of the chick embryo chorioallantoic membrane (CAM). The CAM assay protocol was developed to monitor the metastatic properties of CTCL cells and the effects of Resminostat and/or Ruxolitinib in vivo. In the spontaneous CAM assays, Resminostat and Ruxolitinib treatment inhibited the cell proliferation (p < 0.001) of MyLa and SeAx, and induced cell apoptosis (p < 0.005, p < 0.001, respectively). Although monotherapies reduced the size of primary tumors in the metastasis CAM assay, the drug combination exhibited a significant inhibition of primary tumor size (p < 0.0001). Furthermore, the combined treatment inhibited the intravasation of MyLa (p < 0.005) and SeAx cells (p < 0.0001) in the organs, as well as their extravasation to the liver (p < 0.0001) and lung (p < 0.0001). The drug combination also exerted a stronger inhibitory effect in migration (p < 0.0001) rather in invasion (p < 0.005) of both MyLa and SeAx cells. It further reduced p-p38, p-ERK, p-AKT, and p-STAT in MyLa cells, while it decreased p-ERK and p-STAT in SeAx cells in CAM tumors. Our data demonstrated that the CAM assay could be employed as a preclinical in vivo model in CTCL for pharmacological testing. In agreement with previous in vitro data, the combination of Resminostat and Ruxolitinib was shown to exert antitumor effects in CTCL in vivo. View Full-Text
Keywords: chicken chorioallantoic membrane; CAM; MyLa; SeAx; Resminostat; Ruxolitinib; JAKi; HDACi; intravasation; extravasation; metastasis chicken chorioallantoic membrane; CAM; MyLa; SeAx; Resminostat; Ruxolitinib; JAKi; HDACi; intravasation; extravasation; metastasis
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MDPI and ACS Style

Karagianni, F.; Piperi, C.; Casar, B.; de la Fuente-Vivas, D.; García-Gómez, R.; Lampadaki, K.; Pappa, V.; Papadavid, E. Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma. Cancers 2022, 14, 1070. https://doi.org/10.3390/cancers14041070

AMA Style

Karagianni F, Piperi C, Casar B, de la Fuente-Vivas D, García-Gómez R, Lampadaki K, Pappa V, Papadavid E. Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma. Cancers. 2022; 14(4):1070. https://doi.org/10.3390/cancers14041070

Chicago/Turabian Style

Karagianni, Fani, Christina Piperi, Berta Casar, Dalia de la Fuente-Vivas, Rocío García-Gómez, Kyriaki Lampadaki, Vasiliki Pappa, and Evangelia Papadavid. 2022. "Combination of Resminostat with Ruxolitinib Exerts Antitumor Effects in the Chick Embryo Chorioallantoic Membrane Model for Cutaneous T Cell Lymphoma" Cancers 14, no. 4: 1070. https://doi.org/10.3390/cancers14041070

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