当前位置： SCI文献检索 > JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY期刊下所有文献 > Growth inhibitory effect of dihydroartemisinin on Bcr/Abl+ chronic myeloid leukemia K562 cells involve AKT, ERK and NF-κB modulation.

Growth inhibitory effect of dihydroartemisinin on Bcr/Abl+ chronic myeloid leukemia K562 cells involve AKT, ERK and NF-κB modulation.

Abstract：

PURPOSE:In our previous publication, we have shown that dihydroartemisinin could significantly inhibit the growth of CML K562 cells by its anti-proliferative and inducing apoptotic effects. Given the pivotal effect of Bcr/Abl tyrosine kinase and its downstream signal factors on CML cell proliferation and survival, we extend our study to investigate the effect of DHA on Bcr/Abl and related signal factors to further illuminate the possible mechanisms of the effect of DHA on CML cells. METHODS:The expression of Bcr/Abl was analyzed with PCR and Western blotting methods at both mRNA and protein levels. Measurement of protein expression and tyrosine phosphorylation activity of Bcr/Abl, AKT, ERK1/2, NF-κB and cytochrome c were performed with Western blotting and immunoprecipitation methods. Using the activity kits analyzed the activity of caspase 9 and caspase 3. RESULTS:The treatment with DHA results in a significant suppression on Bcr/Abl expression and leads to a concentration-dependent reduction on the Bcr/Abl tyrosine activity. Moreover, it also results in a strong influence on the downstream signal factors of Bcr/Abl, which includes inhibition of tyrosine kinase activity of AKT and ERK1/2, suppression of NF-κB protein expression, promotion of the cytochrome c release and the consequential activation of caspase 3/9 in CML K562 cells. CONCLUSIONS:Together with our previous report, our data show that the growth inhibitory effect of DHA on CML cells might be due to the influence on Bcr/Abl expression and its downstream signal factors. DHA might be a potential novel anti-CML drug candidate and worthy of further study.

journal_name

J Cancer Res Clin Oncol

journal_title

Journal of cancer research and clinical oncology

authors

Lee J,Zhang G,Wu X,Xu F,Zhou J,Zhang X

doi

10.1007/s00432-012-1292-1

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

2095-102

issue

12

eissn

0171-5216

issn

1432-1335

journal_volume

138

pub_type

杂志文章

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