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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

All-trans retinoic acid synergizes with topotecan to suppress AML cells via promoting RARα-mediated DNA damage

Authors: Zhifei Xu, JinJin Shao, Lin Li, Xueming Peng, Min Chen, Guanqun Li, Hao Yan, Bo Yang, Peihua Luo, Qiaojun He

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Chemotherapy is the only therapy option for the majority of AML patients, however, there are several limitations for this treatment. Our aim was to find a new chemotherapy strategy that is more effective and less toxic.

Methods

MTT assays and a xenograft mouse model were employed to evaluate the synergistic activity of all-trans retinoic acid (ATRA) combined with topotecan (TPT). Drug-induced DNA damage and apoptosis were determined by flow cytometry analysis with PI and DAPI staining, the comet assay and Western blots. Short hairpin RNA (shRNA) and a RARα plasmid were used to determine whether RARα expression influenced DNA damage and apoptosis.

Results

We found that ATRA exhibited synergistic activity in combination with Topotecan in AML cells, and the enhanced apoptosis induced by Topotecan plus ATRA resulted from caspase pathway activation. Mechanistically, ATRA dramatically down regulated RARα protein levels and led to more DNA damage and ultimately resulted in the synergism of these two agents. In addition, the increased antitumor efficacy of Topotecan combined with ATRA was further validated in the HL60 xenograft mouse model.

Conclusions

Our data demonstrated, for the first time, that the combination of TPT and ATRA showed potential benefits in AML, providing a novel insight into clinical treatment strategies.
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Metadata
Title
All-trans retinoic acid synergizes with topotecan to suppress AML cells via promoting RARα-mediated DNA damage
Authors
Zhifei Xu
JinJin Shao
Lin Li
Xueming Peng
Min Chen
Guanqun Li
Hao Yan
Bo Yang
Peihua Luo
Qiaojun He
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-2010-6

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