当前位置： SCI文献检索 > EUROPEAN JOURNAL OF HAEMATOLOGY期刊下所有文献 > Homoharringtonine affects the JAK2-STAT5 signal pathway through alteration of protein tyrosine kinase phosphorylation in acute myeloid leukemia cells.

Homoharringtonine affects the JAK2-STAT5 signal pathway through alteration of protein tyrosine kinase phosphorylation in acute myeloid leukemia cells.

Abstract：

OBJECTIVES:Homoharringtonine (HHT) was efficient in therapying patients with acute myeloid leukemia (AML) in China, but little is known about the mechanism of its action. As the abnormal activation of JAK2 associated pathway is important to AML, we try to explore the effect of HHT on JAK2-STAT pathway in AML cells, thus supplying theoretical basis for wider use of HHT. METHODS:The cell viability was tested by MTT. Apoptosis was tested by flow cytometry. RT-PCR was used to measure the expression of JAK2, STAT5 and the effect gene Bcl-xL. The signal proteins such as p-JAK2, p-STAT5, p-AKT, p-ERK activated by abnormal activated JAK2 were tested by Western blotting. RESULTS:HHT obviously inhibited the viability of primary AML cells and AML cell lines HEL, K562 and HL-60 cells, AnnexinV-PI double staining confirmed early apoptosis in a dose-dependent manner. In immunoblotting analysis, when AML cells were affected by HHT for 6 h (much ahead of the time when apoptosis could be induced). The expressions of p-JAK2, p-STAT5, and p-AKT were down-regulated, while the total JAK2, STAT5 and AKT protein levels were stable. There were no changes in p-ERK and BcL-xL proteins. When it prolonged to 24 h, Bcl-xL decreased obviously. Similar results were obtained by using JAK2 specific inhibitor AG490. CONCLUSIONS:HHT possibly acts as a broad-spectrum PTK inhibitor and inhibits the phosphorylation of the signal proteins caused by oncogenic proteins such as JAK2V617F, BCR/ABL, thus blocking the survival and proliferative signal pathway of malignant cells.

journal_name

Eur J Haematol

journal_title

European journal of haematology

authors

Tong H,Ren Y,Zhang F,Jin J

doi

10.1111/j.1600-0609.2008.01116.x

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

259-66

issue

4

eissn

0902-4441

issn

1600-0609

pii

EJH1116

journal_volume

81

pub_type

杂志文章

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