地西他滨（5-氮杂-2'-脱氧胞苷，5-aza-CdR）与伏立诺他（琥珀酰亚胺基羟肟酸，SAHA）对肝癌 HLE 和 LCL-PI 11 细胞系中 DNMT1、DNMT3a 和 DNMT3b、HDAC1-3、SOCS1、SOCS3、JAK2 和 STAT3 基因表达的影响。

Effect of Decitabine (5-aza-2'-deoxycytidine, 5-aza-CdR) in Comparison with Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) on DNMT1, DNMT3a and DNMT3b, HDAC 1-3, SOCS 1, SOCS 3, JAK2, and STAT3 Gene Expression in Hepatocellular Carcinoma HLE and LCL-PI 11 Cell Lines.

机构信息

Research Center for Non-Communicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran.

Departments of Anatomical Sciences, Jahrom University of Medical Sciences, Jahrom, Iran.

出版信息

Asian Pac J Cancer Prev. 2021 Jul 1;22(7):2089-2098. doi: 10.31557/APJCP.2021.22.7.2089.

BACKGROUND

Epigenetic alterations play an important role in tumorigenesis. Hypermethylation of CpG islands within the promoter regions of tumor suppressor genes (TSGs) and histone deacetylation lead to the silencing of the genes resulting in cancer induction. The suppressor of cytokine signaling (SOCS) family is an important negative regulator of cytokine signaling and deregulation of this family has been reported in several cancers, the protein of the SOCS family inhibit the cytokine-activated Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway to modulate cellular responses. Previously, we evaluated the effects of DNA demethylating agents and histone deacetylase inhibitors on hepatocellular carcinoma (HCC). The current study aimed to investigate the effect of decitabine (5-aza-2'-deoxycytidine, 5-aza-CdR) in comparison to vorinostat (suberoylanilide hydroxamic acid, SAHA) on DNMT1, DNMT3a and DNMT3b, HDAC 1-3, SOCS 1, SOCS 3, JAK2, and STAT3 gene expression, cell growth inhibition, and apoptosis induction of HCC HLE and LCL-PI 11 cell lines.

MATERIAL AND METHODS

The HLE and LCL-PI 11 cells were treated with 5-aza-CdR and SAHA and then the MTT assay, flow cytometry assay, and quantitative real-time RT-PCR were achieved to determine cell viability, cell apoptosis, and relative gene expression respectively.

RESULTS

The result indicated that both compounds inhibited cell growth, induced apoptosis, and down-regulated DNMT1, DNMT3a DNMT3b, HDAC 1-3, JAK2, and STAT3 and up-regulated HDAC 1-3, SOCS 1, and SOCS 3 genes expression significantly. The apoptotic effect of SAHA was stronger than that of 5-Aza-CdR.

CONCLUSION

5-Aza-CdR and SAHA can induce cell growth inhibition and apoptosis induction through the JAK/STAT pathway.

背景

表观遗传改变在肿瘤发生中起着重要作用。肿瘤抑制基因（TSGs）启动子区域内 CpG 岛的高甲基化和组蛋白去乙酰化导致基因沉默，从而诱导癌症。细胞因子信号转导抑制因子（SOCS）家族是细胞因子信号转导的重要负调控因子，该家族的失调已在多种癌症中报道，SOCS 家族的蛋白抑制细胞因子激活的 Janus 激酶/信号转导和转录激活物（JAK/STAT）信号通路，从而调节细胞反应。先前，我们评估了 DNA 去甲基化剂和组蛋白去乙酰化酶抑制剂对肝细胞癌（HCC）的影响。本研究旨在研究地西他滨（5-氮杂-2'-脱氧胞苷，5-aza-CdR）与伏立诺他（琥珀酰亚胺基羟肟酸，SAHA）相比对 DNMT1、DNMT3a 和 DNMT3b、HDAC1-3、SOCS1、SOCS3、JAK2 和 STAT3 基因表达、细胞生长抑制和 HCC HLE 和 LCL-PI11 细胞系凋亡诱导的影响。