Effect of valproic acid on SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A, and SOCS5B in hepatocellular carcinoma HepG2 cell line

Background and aim: Aberrant activation of diverse intracellular signaling pathways involved in differentiation, cell growth, apoptosis. These pathways include known oncogenic pathways such as Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. The JAK/STAT signaling pathway plays an important role in many cellular functions. This pathway can be activated by various cytokines. Suppressors of cytokine signaling (SOCSs) play pivotal roles in immune regulation. Recent studies have indicated that histone deacetylation of SOCSs genes, as tumor suppressor genes (TSGs), leads to gene silencing and induction of numerous cancers such as hepatocellular carcinoma (HCC). Histone deacetylase inhibitors (HDACIs) act against HDACs. Previously, we reported the effect of HDACIs trichostatin A (TSA) and valproic acid (VPA) on colon cancer and hepatocellular carcinoma (HCC). Besides, we reported the effect of VPA on SOCS-1 and SOCS-3 gene expression in colon carcinoma. The current study aimed to investigate the effect of VPA on SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A, and SOCS5B on the HCC HepG2 cell line. Materials and Methods: The HepG2 cells were treated with VPA. To determine cell viability, cell apoptosis, and gene expression, MTT assay, flow cytometry, and Real-time quantitative RT-PCR (qRT-PCR) were done respectively. Results: VPA inhibited cell viability, induced apoptosis, up-regulated SOCS1 and SOCS3, and down-regulated JAK1, JAK2, STAT3, STAT5A, and STAT5B significantly. Conclusion: VPA can induce apoptosis in the HCC HepG2 cell line through JAK/STAT signaling pathway.