Abstract：
:Acute myeloid leukemia (AML) arises from neoplastic transformation of hematopoietic stem and progenitor cells, and resistance to conventional chemotherapy remains one of the greatest challenges in treating the disease. Extensive data have demonstrated that angiogenesis is associated with AML progression and chemotherapy resistance. Thus, targeting angiogenesis may be a promising approach for AML treatment. In this study, we investigated the effectiveness of CS2164 (named as Chiauranib), a novel receptor tyrosine kinase inhibitor, in AML cells. Our results illustrated that CS2164 significantly suppressed cell proliferation and abolished clonogenicity in AML cells in a dose- and time-dependent manner. Meanwhile, CS2164 markedly induced apoptosis of AML cell lines and primary AML cells from 42 adult patients. Furthermore, we found that CS2164 has a comprehensive activity against AML irrespective of disease status and genetic mutations. Also, CS2164 suppressed AML growth in xenograft models in vivo. Mechanistically, CS2164-induced cytotoxicity was closely associated with inhibition of VEGFR2 and its downstream signaling cascades, including Src/Fyn/p38 and Erk/MEK. In conclusion, our study indicates that CS2164 exerts anti-leukemia effect by inducing apoptosis through suppressing the VEGFR2 pathway, supporting a potential role for CS2164 in the treatment of AML.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Deng M,Zhao H,Chen Q,Zhao J,Shi Y,Yu L,Fang Z,Xu Bdoi
10.1016/j.ejphar.2019.03.041subject
Has Abstractpub_date
2019-06-15 00:00:00pages
193-200eissn
0014-2999issn
1879-0712pii
S0014-2999(19)30202-Xjournal_volume
853pub_type
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journal_title：European journal of pharmacology
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doi：10.1016/j.ejphar.2003.11.041
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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