1. Retinoic Acid Receptor-β Gene Reexpression and Biological Activity in SHI-1 Cells after Combined Treatment with 5-Aza-2′-Deoxycytidine and All-Trans Retinoic Acid.
- Author
-
Xiang, Lili, Wang, Rong, Wei, Jiang, Qiu, Guoqiang, Cen, Jiannong, Hu, Shaoyan, Xie, Xiaobao, Chen, Zixing, and Gu, Weiying
- Subjects
- *
RETINOIC acid receptors , *GENE expression , *ACUTE myeloid leukemia treatment , *COMBINATION drug therapy , *DEOXYCYTIDINE , *APOPTOSIS inhibition , *DNA methylation , *THERAPEUTICS - Abstract
Background: This study was conducted to determine the antineoplastic activities of 5-aza-2′-deoxycytidine (decitabine; DAC) and all-trans retinoic acid (ATRA), administered either alone or in combination, on in vitro cultured SHI-1 cells as well as their effects on the expression of the tumor suppressor gene p16INK4a (p16) and the retinoic acid receptor (RAR)-β. Methods: Cellgrowth inhibition, differentiation and apoptosis were determined in SHI-1 cells treated with DAC and/or ATRA, and the combination index of the two compounds was calculated. Methylation of the p16 and RAR-β genes in SHI-1 cells was detected by methylation-specific polymerase chain reaction (PCR). Real-time quantitative reverse transcriptase PCR was used to detect mRNA expression of the p16 and RAR-β genes, and Western blot analysis was performed for protein expression. Results: The drug combination had a synergistic effect on growth inhibition, differentiation and apoptosis of SHI-1 cells, and the effects of DAC and ATRA weredependent on time. DAC, either alone or in combination with ATRA, induced demethylation of the genes p16 and RAR-β, whereas ATRA alone had no effect on methylation. The RAR-β gene was reexpressed following DAC-ATRA combination treatment, and both agents had no effect on p16 expression. Conclusion: The results revealed that DAC used in combination with ATRA has significant clinical potential in the treatment of acute monocytic leukemia. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF