Wang Ming-Ming, Zhu Qi, Ren Zhi-Hong, Zou Li-Fang, Dou Hong-Ju, Hu Jun-Pei
Department of Hematology, Shanghai Ninth People Hospital, Shanghai Institute of Hematology, Shanghai 200011, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008 Oct;16(5):1064-8.
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).
本研究旨在探讨三氧化二砷（As₂O₃）对多发性骨髓瘤细胞系U266、RPMI8226中socs-1基因甲基化状态的影响。采用MTT法检测细胞活力。用甲基化特异性PCR检测socs-1基因的甲基化状态。用实时PCR测定socs-1基因mRNA的表达。通过流式细胞术分析细胞凋亡。结果表明，在骨髓瘤细胞系U266、RPMI8226中观察到socs-1基因的CpG岛发生高甲基化，且无socs-1表达。与野生型细胞系相比，各骨髓瘤细胞系在暴露于As₂O₃ 72小时后，socs-1基因mRNA的表达显著增加（p < 0.05）。并且细胞增殖受到显著抑制，早期凋亡率和晚期凋亡率均呈剂量依赖性增加。结论是As₂O₃可能诱导socs-1去甲基化并上调该基因的表达。本研究为探索As₂O₃诱导细胞凋亡的可能机制及As₂O₃治疗多发性骨髓瘤提供了新的思路和方向。
