Nanocarrier mediated entinostat and oxaliplatin combination therapy displayed enhanced efficacy against pancreatic cancer.

Autor: Giri PM; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, United States., Kumar A; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, United States., Salu P; Department of Biological Sciences, North Dakota State University, Fargo, ND 58105, United States., Sathish V; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, United States., Reindl K; Department of Biological Sciences, North Dakota State University, Fargo, ND 58105, United States., Mallik S; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, United States., Layek B; Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58105, United States. Electronic address: buddhadev.layek@ndsu.edu.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Jun; Vol. 175, pp. 116743. Date of Electronic Publication: 2024 May 16.
DOI: 10.1016/j.biopha.2024.116743
Abstrakt: Pancreatic cancer is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 12%. The poor prognosis of pancreatic cancer is primarily attributed to the lack of early detection, the aggressiveness of the disease, and its resistance to conventional chemotherapeutics. The use of combination chemotherapy targeting different key pathways has emerged as a potential strategy to minimize drug resistance while improving therapeutic outcomes. Here, we evaluated a novel approach to treating pancreatic cancer using entinostat (ENT), a selective class I and IV HDAC inhibitor, and oxaliplatin (OXP) administered at considerably lower dosages. Combination therapy exhibited strong synergistic interaction against human (PANC-1) and murine (KPC) pancreatic cancer cells. As expected, ENT treatment enhanced acetylated histone H3 and H4 expression in treated cells, which was even augmented in the presence of OXP. Similarly, cells treated with a combination therapy showed higher expression of cleaved caspase 3 and increased apoptosis compared to monotherapy. To further improve the efficacy of the combination treatment, we encapsulated OXP and ENT into bovine serum albumin and poly(lactic-co-glycolic) acid nanoparticles. Both nanocarriers showed suitable physicochemical properties with respect to size, charge, polydispersity index, and loading. Besides, the combination of OXP and ENT nanoparticles showed similar or even better synergistic effects compared to free drugs during in vitro cytotoxicity and colony formation assays towards pancreatic cancer cells.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors report financial support was provided by National Institute of General Medical Sciences
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
Databáze: MEDLINE
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