All-Trans Retinoic Acid and Decitabine Synergistically Induce Anti-Leukemia Effect on U937 Cell Line and Newly Diagnosed Elder AML Patients

• Published in: Zhongguo shi yan xue ye xue za zhi Vol. 26; no. 4; p. 964
• Main Authors: Dong, Wei-Min, Cao, Yang, Xiang, Li-Li, Lin, Yan, Liu, Yue, Cen, Jian-Nong, Xie, Xiao-Bao, Gu, Wei-Ying
• Format: Journal Article
• Language: Chinese
• Published: China 01.08.2018
• Subjects: Azacitidine - analogs & derivatives; Decitabine; Humans; Leukemia, Myeloid, Acute; Tretinoin; U937 Cells
• ISSN: 1009-2137
• DOI: 10.7534/j.issn.1009-2137.2018.04.004

To investigate the effect of all transretinoicacid(ATRA) combined with decitabine (5-Aza-2'-deoxycytidine;DAC) on DNA methylation and gene expression of p16INK4a (p16) and retinoic acid receptor β (RARβ), and to explore their combined anti neoplastic effect on U937 cells and newly diagnose delder acute myeloid leukemia(AML) patients. The expression levels of p16 and RARβ were determined by qRT-PCR and Western blot. Methylation-specific PCR was used to analyze their methylation status. WST-1 and flow cytometry were performed to detect growth inhibition, differentiation, apoptosis and cell cycle of U937 cells respectively. The expression p16 and RARβ was down-regulated by promoter hypermethylation in newly diagnose delder AML patients and U937 cells. Combination treatment of ATRA and DAC induced DNA hypomethylation as well as gene expression of p16 and RARβ, which contributed to the growth inhibition, differentiation, apoptosis and cell cycle arrest of U937 cells. In addition for elder AML patients intolerable