۵-Fluorouracil-Loaded PLGA Declined Expression of Pro-Inflammatory Genes IL-۹, IL-۱۷A, IL-۲۳ and IFN- γ in the HT-۲۹ Colon Cancer Cell Line

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 ۵-fluorouracil (۵-FU) on their expression might shed light on development of novel combinational therapies. This study aimed to  encapsulate ۵-FU into PLGA  and evaluate their effects on the expression of pro-inflammatory genes IL-۹, IL-۱۷-A, IL-۲۳, and IFN-γ in the HT-۲۹ cells. Methods: PLGA-۵-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 IC۵۰ was identified. HT-۲۹ cells were treated with different concentrations of the PLGA-۵-FU NPs for ۴۸ hours and, gene expression levels were analyzed by qRT-PCR. Results: DLS and AFM analysis revealed that the prepared PLGA-۵-FU NPs were negatively charged spherical-shaped particles with a mean size of ۲۱۵.۹ ± ۴۳.۳ nm. PLGA-۵-FU NPs impacted the viability of HT-۲۹ cells in a dose- and time-dependent manner. The qRT-PCR results revealed a dose-dependent decrease in the expression of IL-۹, IL-۱۷A, IL-۲۳ and IFN-γ genes, and their expressions were significantly different in both ۱۰ and ۲۰ µg/mL treated groups compared to the control. However, although the treatment of HT-۲۹ cells with ۲۰ µg/mL free ۵-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group. Conclusions: PLGA-۵-FU NPs significantly suppressed expression of the IL-۹, IL-۱۷A, IL-۲۳ and IFN-γ genes, and the encapsulation of ۵-FU into PLGA improved considerably impact of the ۵-FU on the HT-۲۹ cells.

Keywords:

Cancer therapy , Colorectal cancer , Fluorouracil , Polylactic Acid-Polyglycolic Acid Copolymer (PLGA) , Pro-inflammatory cytokine.