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Volume 12, Issue 4 (Vol.12 No.4 Jan 2024)
rbmb.net 2024, 12(4): 664-673 |
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Kadhum Kharmeet B, Khalaj-Kondori M, Hosseinpour feizi M A, Hajavi J. 5-Fluorouracil-Loaded PLGA Declined Expression of Pro-Inflammatory Genes IL-9, IL-17A, IL-23 and IFN- γ in the HT-29 Colon Cancer Cell Line. rbmb.net 2024; 12 (4) :664-673
URL: http://rbmb.net/article-1-1324-en.html
URL: http://rbmb.net/article-1-1324-en.html
Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Abstract: (500 Views)
Background: Pro-inflammatory cytokines play critical roles in cancer pathobiology and have been considered potential targets for cancer management and therapy. Understanding the impact of cancer therapeutics such as 5-fluorouracil (5-FU) on their expression might shed light on development of novel combinational therapies. This study aimed to encapsulate 5-FU into PLGA and evaluate their effects on the expression of pro-inflammatory genes IL-9, IL-17-A, IL-23, and IFN-γ in the HT-29 cells.
Methods: PLGA-5-FU NPs were constructed and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The cytotoxicity was evaluated by MTT test and, the IC50 was identified. HT-29 cells were treated with different concentrations of the PLGA-5-FU NPs for 48 hours and, gene expression levels were analyzed by qRT-PCR.
Results: DLS and AFM analysis revealed that the prepared PLGA-5-FU NPs were negatively charged spherical-shaped particles with a mean size of 215.9 ± 43.3 nm. PLGA-5-FU NPs impacted the viability of HT-29 cells in a dose- and time-dependent manner. The qRT-PCR results revealed a dose-dependent decrease in the expression of IL-9, IL-17A, IL-23 and IFN-γ genes, and their expressions were significantly different in both 10 and 20 µg/mL treated groups compared to the control. However, although the treatment of HT-29 cells with 20 µg/mL free 5-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group.
Conclusions: PLGA-5-FU NPs significantly suppressed expression of the IL-9, IL-17A, IL-23 and IFN-γ genes, and the encapsulation of 5-FU into PLGA improved considerably impact of the 5-FU on the HT-29 cells.
Methods: PLGA-5-FU NPs were constructed and characterized by Dynamic Light Scattering (DLS) and Atomic Force Microscopy (AFM). The cytotoxicity was evaluated by MTT test and, the IC50 was identified. HT-29 cells were treated with different concentrations of the PLGA-5-FU NPs for 48 hours and, gene expression levels were analyzed by qRT-PCR.
Results: DLS and AFM analysis revealed that the prepared PLGA-5-FU NPs were negatively charged spherical-shaped particles with a mean size of 215.9 ± 43.3 nm. PLGA-5-FU NPs impacted the viability of HT-29 cells in a dose- and time-dependent manner. The qRT-PCR results revealed a dose-dependent decrease in the expression of IL-9, IL-17A, IL-23 and IFN-γ genes, and their expressions were significantly different in both 10 and 20 µg/mL treated groups compared to the control. However, although the treatment of HT-29 cells with 20 µg/mL free 5-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group.
Conclusions: PLGA-5-FU NPs significantly suppressed expression of the IL-9, IL-17A, IL-23 and IFN-γ genes, and the encapsulation of 5-FU into PLGA improved considerably impact of the 5-FU on the HT-29 cells.
Keywords: Cancer therapy, Colorectal cancer, Fluorouracil, Polylactic Acid-Polyglycolic Acid Copolymer (PLGA), Pro-inflammatory cytokine.
Type of Article: Original Article |
Subject:
Molecular Biology
Received: 2024/01/15 | Accepted: 2024/06/2 | Published: 2024/07/2
Received: 2024/01/15 | Accepted: 2024/06/2 | Published: 2024/07/2
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