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'); Reports of Biochemistry and Molecular Biology rbmb.net Basic Sciences http://rbmb.net 1 admin 2322-3480 2322-3480 10.61882/rbmb en jalali 1402 11 1 gregorian 2024 2 1 12 4 online 1 fulltext
en 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 زیست شناسی ملکولی Molecular Biology مقالات اصلی Original Article <div class="WordSection1"> <div style="text-align: justify;"><span style="page:WordSection1"><span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><b><i><span lang="EN-GB" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Background:</span></span></span></i></b> <span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"><span style="letter-spacing:-.1pt">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&nbsp; en</span></span></span></span></span></span></span></span></span></span></span><span lang="EN-CA" style="font-size:12.0pt"><span style="line-height:110%"><span new="" roman="" style="font-family:" times=""><span style="color:black"><span style="letter-spacing:-.1pt">capsulate 5-FU into PLGA </span></span></span></span></span><span style="page:WordSection1"><span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"><span style="letter-spacing:-.1pt">&nbsp;and evaluate their effects on the expression of pro-inflammatory genes <i>IL-9, IL-17-A, IL-23</i>, and <i>IFN-&gamma;</i> in the HT-29 cells.</span></span></span></span></span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><b><i><span lang="EN-GB" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Methods:</span></span></span></i></b><b> </b><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">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 IC<sub>50</sub> 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. </span></span></span></span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><b><i><span lang="EN-GB" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Results:</span></span></span></i></b><b> </b><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">DLS and AFM<b> </b>analysis revealed that the prepared PLGA-5-FU NPs were negatively charged spherical-shaped particles with a mean size of 215.9 &plusmn; 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 <i>IL-9, IL-17A, IL-23</i> and <i>IFN-</i></span></span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">&gamma;</span></span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"> genes, and their expressions were significantly different in both 10 and </span></span></span><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">20 &micro;g/mL </span></span></span><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">treated groups compared to the control.</span></span></span><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"> However, although the treatment of HT-29 cells with 20 &micro;g/mL free 5-FU resulted in decreased expression of the studied genes, the differences were not statistically significant compared to the control group. </span></span></span></span></span></span></span></span></span><br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><b><i><span lang="EN-GB" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">Conclusions:</span></span></span></i></b><b> </b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">PLGA-5-FU NPs significantly suppressed expression of the </span></span></span><i><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">IL-9, IL-17A, IL-23</span></span></span></i><span lang="EN-CA" style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"> and <i>IFN-</i></span></span></span><i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black">&gamma;</span></span></span></i><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"> genes, and the encapsulation of 5-FU into PLGA improved considerably impact of the 5-FU on the HT-29 cells. </span></span></span></span></span></span></span></span></span><br> <br> <span style="font-size:10pt"><span style="text-justify:kashida"><span style="text-kashida:0%"><span style="line-height:normal"><span style="tab-stops:396.55pt"><span style="font-family:Calibri,sans-serif"><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""><span style="color:black"></span></span></span></span></span></span></span></span></span></span></div> <div align="center" style="text-align:center"> <hr align="center" noshade="noshade" size="2" style="color:#0f243e" width="100%" ></div> </div> <div style="text-align: justify;"><div aria-label="Page Break" class="cke_pagebreak" contenteditable="false" data-cke-display-name="pagebreak" data-cke-pagebreak="1" style="page-break-after:always" title="Page Break"></div></div> Cancer therapy, Colorectal cancer, Fluorouracil, Polylactic Acid-Polyglycolic Acid Copolymer (PLGA), Pro-inflammatory cytokine. 664 673 http://rbmb.net/browse.php?a_code=A-10-1427-2&slc_lang=en&sid=1 Basheer Kadhum Kharmeet 100319475328460020264 100319475328460020264 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Mohammad Khalaj-Kondori khalaj@tabrizu.ac.ir 100319475328460020265 100319475328460020265 Yes Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Mohammad Ali Hosseinpour feizi 100319475328460020266 100319475328460020266 No Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran. Jafar Hajavi 100319475328460020267 100319475328460020267 No Department of Microbiology, Faculty of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Science, Gonabad, Iran & Innovative Medical Research Center, Mashhad Branch, Islamic Azad University, Mashhad, Iran.