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The Effect of Valproic Acid Drug on the Expression of SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A and STAT5B Genes in HepG2 Cell Line Liver Cancer
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M Sanai Jahormi1    , F Kaousi 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: (1202 Views) |
Background & aim: Aberrant activation of various intracellular pathways is involved in differentiation, growth, apoptosis and cell survival. Different known intracellular pathways such as JAK/STAT cause tumor genesis and cancer development. This pathway plays an important role in various cellular functions and is activated by cytokines. Suppressors of cytokine signaling (SOCSs) genes play a pivotal role in regulating the immune system. Therefore, the aim of the research was to determine the effect of valproic acid drug on the expression of SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A and STAT5B genes in HepG2 cell line liver cancer.
Methods: In the present experimental study conducted in 2019, HepG2 liver cancer cells were purchased from Pasteur Institute and the overlapping of the cells reached about 80%. Using trypsin, the cells were collected and after washing, they were cultured in 96-well plates. After 24 hours of cell culture, the culture medium was drained and the medium containing valproic acid drug with different concentrations (0, 1, 5, 7.5, 10, 15, 20 and 25 μmol) was replaced (solvent only control group). They received the drug, DMSO). After 24 and 48 hours, the cells were washed with PBS solution. MTT technique was used to determine cell viability. To determine the amount of apoptotic cells and gene expression, the cells were treated with valproic acid with a concentration of 6.643 μmol for 24 hours and 5.401 μmol for 48 hours, and after 24 and 48 hours, flow cytometry and real-time techniques were used for Determination of apoptotic cells and expression of SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A and STAT5B genes were used. The collected data were analyzed using one-way analysis of variance and Turkey’s test.
Results: Valproic acid significantly increased the expression of SOCS1 and SOCS3 genes, decreased the expression of JAK1, JAK2, STAT3, STAT5A and STAT5B genes and inhibited cell growth. This combination significantly caused apoptosis (p<0.001). The percentage of apoptotic cells after 24 and 48 hours was 22.38 and 50.3, respectively. The maximum amount of apoptosis was observed after 48 hours.
Conclusion: Valproic acid can induce apoptosis in HepG2 liver cancer through JAK/STAT pathway. Valproic acid seems to exert its apoptotic effect by decreasing the expression of JAK1, JAK2, STAT3, STAT5B genes and increasing SOCS1 and SOCS3 genes.
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| Keywords: Valproic acid, JAK/STAT pathway, Liver cancer, Apoptosis |
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Full-Text [PDF 1136 kb]
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Type of Study: Research |
Subject:
Special
Received: 2021/12/9 | Accepted: 2022/05/17 | Published: 2022/05/18
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Sanai Jahormi M, Kaousi F. The Effect of Valproic Acid Drug on the Expression of SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A and STAT5B Genes in HepG2 Cell Line Liver Cancer. armaghanj 2022; 27 (3) :336-348 URL: http://armaghanj.yums.ac.ir/article-1-3217-en.html
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