Apatinib exhibits anti-leukemia activity in preclinical models of acute lymphoblastic leukemia

Journal of Translational Medicine
Manman DengBing Xu

Abstract

Acute lymphoblastic leukemia (ALL) is a clonal malignant disorder characterized by an uncontrolled proliferation of immature B or T lymphocytes. Extensive studies have suggested an involvement of angiogenesis signaling in ALL progression and resistance to treatment. Thus, targeting angiogenesis with anti-angiogenic drugs may be a promising approach for ALL treatment. In this study, we investigated the effectiveness of Apatinib, a novel receptor tyrosine kinase inhibitor selectively targeting VEGFR-2 in ALL cells. ALL cell lines were treated with different concentration of Apatinib and then CCK8 assay, flow cytometry were used to determine the IC50 value and cell apoptosis, respectively. The effect of Apatinib against primary ALL cells from 11 adult patients and normal counterparts were also analyzed by apoptosis with flow cytometry. Next, we used western bolting and mass cytometry (CyTOF) assay to explore the underlying mechanism of the cytotoxicity of Apatinib. Finally, the anti-leukemia activity was further evaluated in an in vivo xenograft model of ALL. Our results showed that Apatinib significantly inhibited cell growth and promoted apoptosis in both B and T lineage ALL cell lines in a dose- and time-dependent manner. The I...Continue Reading

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Citations

Sep 4, 2020·Diagnostics·Anca OnaciuIoana Berindan-Neagoe
Nov 18, 2020·World Journal of Hepatology·Xi-Hao ZhangTi Zhang
Jan 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chinmayee Sethy, Chanakya Nath Kundu
Jun 26, 2021·Cancer Control : Journal of the Moffitt Cancer Center·Fang-Liang HuangChia-Ling Li
Jul 17, 2021·Nature Reviews. Cardiology·Dawn M Fernandez, Chiara Giannarelli

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Methods Mentioned

BETA
flow cytometry
xenograft
X-ray
xenografts

Software Mentioned

GraphPad Prism
[UNK]
FACS C6
SPSS

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