In:
Acta Haematologica, S. Karger AG, Vol. 133, No. 3 ( 2015), p. 279-286
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 This study was conducted to determine the antineoplastic activities of 5-aza-2′-deoxycytidine (decitabine; DAC) and all- 〈 i 〉 trans 〈 /i 〉 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 p16 〈 sup 〉 INK4a 〈 /sup 〉 (p16) and the retinoic acid receptor (RAR)-β. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Cell 〈 b 〉 〈 /b 〉 growth 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 The drug combination had a synergistic effect on growth inhibition, differentiation and apoptosis of SHI-1 cells, and the effects of DAC and ATRA were 〈 b 〉 〈 /b 〉 dependent 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. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 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
Type of Medium:
Online Resource
ISSN:
0001-5792
,
1421-9662
Language:
English
Publisher:
S. Karger AG
Publication Date:
2015
detail.hit.zdb_id:
1481888-7
detail.hit.zdb_id:
80008-9