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Published on: February 1, 2020
[Arsenic trioxide induces socs-1 gene demethylation in myeloma cell lines]
Ming-Ming Wang1, Qi Zhu, Zhi-Hong Ren
1Department of Hematology, Shanghai Ninth People Hospital, Shanghai Institute of Hematology, Shanghai 200011, China.
Abstract:
The aim of this study was to explore the effect of arsenic trioxide (As(2)O(3)) on the methylation status of socs-1 gene in multiple myeloma cell lines U266, RPMI8226. The cell viability was assayed by MTT method. The methylation status of socs-1 gene was detected by methylation specific PCR. The expression of socs-1 gene mRNA was determined with real-time PCR. The cell apoptosis was analyzed by flow cytometry. The results indicated that hypermethylation of CpG island of socs-1 gene was observed without expression of socs-1 in myeloma cell lines U266, RPMI8226. The expression of socs-1 gene mRNA in each myeloma cell line increased significantly after exposure to As(2)O(3) for 72 hours as compared with the cell lines of wild type (p < 0.05). And cell proliferation was significantly inhibited, both early apoptosis and later apoptosis ratios increased in dose-dependent manner. It is concluded that As(2)O(3) may induce socs-1 demethylation and up-regulate the expression of the gene. This study provides a new thought and direction for exploring possible mechanism of cell apoptosis induced by As(2)O(3) and multiple myeloma treatment by As(2)O(3).
Insights
Arsenic trioxide (As(2)O(3)) treatment demethylated the socs-1 gene in multiple myeloma cells, increasing its expression and inducing apoptosis. This suggests As(2)O(3) as a potential therapeutic agent for multiple myeloma.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multiple myeloma is characterized by aberrant gene methylation, affecting tumor suppressor genes.
- The socs-1 gene, crucial for immune regulation, is often silenced by hypermethylation in cancers.
- Arsenic trioxide (As(2)O(3)) has shown anti-cancer properties, but its mechanism in multiple myeloma requires further elucidation.
Purpose of the Study:
- To investigate the impact of As(2)O(3) on socs-1 gene methylation and expression in multiple myeloma cell lines.
- To determine the effect of As(2)O(3)-induced socs-1 modulation on cell viability and apoptosis.
Main Methods:
- Cell viability was assessed using the MTT assay.
- Methylation-specific PCR was employed to analyze socs-1 gene methylation status.
- Real-time PCR quantified socs-1 gene mRNA expression.
- Flow cytometry was used to analyze cell apoptosis.
Main Results:
- Multiple myeloma cell lines (U266, RPMI8226) exhibited hypermethylation and lack of socs-1 expression.
- As(2)O(3) exposure significantly increased socs-1 mRNA expression in a time-dependent manner (72 hours).
- As(2)O(3) treatment inhibited cell proliferation and dose-dependently increased both early and late apoptosis.
Conclusions:
- As(2)O(3) treatment can induce demethylation of the socs-1 gene, leading to its up-regulation.
- The findings suggest a novel mechanism for As(2)O(3)-induced apoptosis in multiple myeloma.
- This study highlights the potential of As(2)O(3) as a therapeutic strategy for multiple myeloma by targeting gene methylation and expression.

