[Effect of low-dose hydroxyurea with sodium butyrate on globin gene expression in human erythroid progenitor cells].
OBJECTIVE
To investigate the effects of combined use of low-dose hydroxyurea (HU) and sodium butyrate (NaB) on the expression of 7 globin genes (zeta, alpha, epsilon, Ggamma, Agamma, delta, and beta) in human erythroid progenitor cells.


METHODS
Human erythroid progenitor cells were cultured using a two-step liquid culture system and treated with HU and NaB either alone or in combination. The inhibitory effects of the agents on the cell growth were monitored with trypan blue exclusion assay, and the changes in the mRNA of the 7 globin genes were detected using RT-PCR.


RESULTS
Low-dose HU combined with NaB resulted in significantly lower inhibition rate of the erythroid progenitor cells than routine dose HU and NaB used alone (28.56% and 38.80%, respectively, P<0.05). Compared with untreated cells (0.653-/+0.092 and 0.515-/+0.048), HU combined with NaB significantly increased the expression of Ggamma-and Agamma- mRNA (1.203-/+0.018 and 0.915-/+0.088, respectively, P<0.05), and HU and NaB used alone produced similar effects (1.305-/+0.016 and 0.956-/+0.029 for HU, and 1.193-/+0.070 and 0.883-/+0.012 for NaB, P>0.05). HU and NaB, either used alone or in combination or at different doses, caused no significant changes in the other globin genes (zeta, alpha, epsilon, delta and beta) (P>0.05).


CONCLUSIONS
Low-dose HU combined with NaB can up-regulate gamma globin gene expression, especially Ggamma-mRNA expression, to decrease the growth inhibition on human erythroid progenitor cells in vitro, but produces no significant effect on the expressions of zeta, alpha, epsilon, delta and beta genes.
Wu
Qian-qian
QQ
Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. wuqq_88@yahoo.com.cn
Qian
Xin-hua
XH
Xu
Mei-jia
MJ
D000755:Anemia, Sickle Cell / Q000235:genetics*; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004920:Erythropoiesis / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D055545:gamma-Globins / Q000235:genetics / Q000378:metabolism*
D002087:Butyrates; D012333:RNA, Messenger; D055545:gamma-Globins; D006918:Hydroxyurea