Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Antitumorigenic Effect of Combination Treatment with BRAF Inhibitor and Cisplatin in Colorectal Cancer In Vitro and In Vivo
Δημιουργός/Συγγραφέας:	Koumaki, Kassandra Skarmalioraki, Salomi [EL] Κοσμίδου, Παρασκευή[EN] Kosmidou, Paraskevi Krikoni, Lida Goulielmaki, Maria [EL] Ζουμπουρλής, Βασίλης[EN] Zoumpourlis, Vassilis [EL] Πίντζας, Αλέξανδρος[EN] Pintzas, Alexander [EL] Σουλιώτης, Βασίλης Λ.[EN] Souliotis, Vassilis L.
Ημερομηνία:	2024
Γλώσσα:	Αγγλικά
ISSN:	2366-3987 2366-3987
DOI:	10.1002/adtp.202400250
Περίληψη:	In colorectal cancer (CRC), BRAF inhibitor (BRAFi) monotherapy appears ineffective, while cisplatin treatment is associated with adverse effects, drug resistance, and reduced efficacy. Herein, a combinatorial approach is being explored to increase the likelihood of effectively killing colorectal cancer cells. The combined effect of BRAFi (PLX4720, Vemurafenib, Dabrafenib, Encorafenib) and cisplatin treatment is examined in BRAFV600E-mutated (RKO, HT29, Colo-205) and BRAFwt (Caco-2) cell lines, as well as in mouse xenografts of RKO cells. Following cisplatin-only treatment, all cell lines show accumulation within subG1 (apoptotic cells) and G2/M phases, as well as phosphorylation of ERK1/2 and H2AX. Following BRAFi-only treatment, BRAFV600E-mutated cells show accumulation within G0/G1 phase, reduced distribution in the S and G2/M phases, inhibition of ERK1/2 phosphorylation, and increased phosphorylation of H2AX. Combined BRAFi and cisplatin treatment synergistically decrease RKO cells viability, reduce phosphorylation of ERK1/2, and increase phosphorylation of H2AX. Importantly, in mouse xenografts of RKO cells, combined PLX4720 and cisplatin treatment show superior therapeutic potential than each monotherapy (P < 0.001). Taken together, in in vitro and in vivo preclinical models, BRAFi and cisplatin combined treatment has shown an improved antitumor effect, rendering it a potential anticancer treatment strategy for BRAF-mutant colon cancer patients.
Τίτλος πηγής δημοσίευσης:	Advanced Therapeutics
Τόμος/Κεφάλαιο:	8
Τεύχος:	1
Θεματική Κατηγορία:	[EL] Μοριακή Βιολογία[EN] Molecular Biology [EL] Βιοχημεία[EN] Biochemistry [EL] Θεραπευτική. Φαρμακολογία[EN] Therapeutics.Pharmacology [EL] Νεοπλάσματα. Όγκοι. Ογκολογία (περ. Καρκίνος, κακινογόνες ουσίες)[EN] Neoplasms. Tumors. Oncology (Incl.cancer, carcinogens)
Λέξεις-Κλειδιά:	BRAF inhibitors BRAFV600E-mutated cells cisplatin colorectal cancer combination therapy mouse xenografts
Χρηματοδότης:	European Regional Development Fund
EU Grant:	Competitiveness, Entrepreneurship and Innovation
EU Grant identifier:	MIS5002398
Κάτοχος πνευματικών δικαιωμάτων:	© 2024 The Author(s). Advanced Therapeutics published by Wiley-VCH GmbH
Όροι και προϋποθέσεις δικαιωμάτων:	This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://doi.org/10.1002/adtp.202400250
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο