[Effect of hydroxyurea combined with interferon-alpha on growth and apoptosis-related oncogene expression of K562 cells].
OBJECTIVE
To observe the effect of hydroxyurea (HU) alone and in combination with interferon-alpha (IFN-alpha) on the cell growth and cell death, and the related oncogene expression of chronic myelogenous leukemia (CML) cell line, K562 cells. To further investigate the molecular basis of combination therapy on CML by chemotherapeutants combined with cytokines.


METHODS
The proliferation and viability of K562 cells were detected by cell-counting and trypan blue dye exclusion test. The levels of bcr-abl, bax and c-myc gene expression in K562 cells incubated for 48 hours were examined using RT-PCR technique.


RESULTS
proliferation was suppressed and cell death process was accelerated by both HU and HU combined with IFN-alpha. HU significantly inhibited bcr-abl gene expression and increased bax gene expression level (both P < 0.05 as compared with that of control). Furthermore, IFN-alpha dose-dependently enhanced the regulatory effects of HU on bcr-abl and bax gene expression. HU alone and in combination with IFN-alpha suppressed slightly c-myc gene expression.


CONCLUSIONS
Both HU and HU combined with IFN-alpha can inhibit cell proliferation and promote cell death or apoptotic cell death by regulating the expression levels of the genes relating to cell proliferation and apoptosis. The molecular mechanism of HU and IFN-alpha synergistically acting on leukemic cells is further elucidated from the expression level of the related genes which control the balance of survival and death or apoptosis of the cells.
Chen
H
H
Research Center for Molecular Biology, Hunan Medical University, Changsha 410078, China.
Luo
Z
Z
Luo
S
S
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology*; D020014:K562 Cells; D009857:Oncogenes / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D016898:Interferon-alpha; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D016044:Fusion Proteins, bcr-abl; D006918:Hydroxyurea