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Evaluation of the Effect of Valproic Acid on JAK/STAT Pathway, SOCS1, SOCS3, Bcl-xL, c-Myc, and Mcl-1 Gene Expression, Cell Growth Inhibition and Apoptosis Induction in Human Colon Cancer HT29 Cell Line
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M Sanaei Jahromi1    , F Kavousi 2 |
1- Non-Communicable Diseases Research Center, Jahrom University of Medical Sciences, Jahrom, Iran
2- Non-Communicable Diseases Research Center, Jahrom University of Medical Sciences, Jahrom, Iran , kavoosifraidoon@gmail.com |
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Abstract: (1478 Views) |
Abstract:
Background & aim: Cytokines are a large family of messenger proteins, which induce various cancers. Cytokines are mediated by Janus kinases (JAKs). Once activated, these kinases phosphorylate the STAT protein (signal transducers and activators of transcription, STAT), and STAT regulates the expression of genes involved in cell differentiation, proliferation, and apoptosis. Defects in the JAK / STAT pathway cause tumorigenesis and cancer. Improper expression of STAT genes impairs the expression and expression of Bcl-xL, c-Myc, Mcl-1, CCND1 and VEGF genes, resulting in uncontrolled cell proliferation and cancer. The aim of the present study was to determine the effect of valproic acid on the expression of JAK1, JAK2, STAT3, STAT5A, STAT5B, SOCS1, SOCS3, Bcl-xL, c-Myc and Mcl-1 genes, cell viability and induction of apoptosis in colon cancer. Cell line was HT29.
Methods: In the present experimental-laboratory study conducted in 2019, the HT 29 colorectal cancer cells were treated with valproic acid. MTT, flow cytometry and real-time techniques were used to determine cell viability, apoptotic cells and gene expression, respectively. The obtained data were analyzed using Prism Graph Pad 8 software.
Results: Valproic acid significantly inhibited cell growth, induced apoptosis, decreased expression of JAK1, JAK2, STAT3, STAT5A, STAT5B, Bcl-xL, c-Myc and Mcl-1 genes and increased the expression of SOCS1 and SOCS3 genes. Alteration in the expression of the above genes inhibited cell proliferation and induced apoptosis in the studied cancer cells.
Conclusion: VPA can induce apoptosis in colon cancer HT29 cell line through JAK/STAT pathway.
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| Keywords: VPA, JAK/STAT, Colon Cancer, Apoptosis |
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Full-Text [PDF 903 kb]
(565 Downloads)
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Type of Study: Research |
Subject:
Special
Received: 2021/03/27 | Accepted: 2021/05/9 | Published: 2021/07/6
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