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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2014

Open Access 01-12-2014 | Research

Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model

Authors: Ke-Zhi Zhang, Qiang-Bo Zhang, Quan-Bao Zhang, Hui-Chuan Sun, Jian-Yang Ao, Zong-Tao Chai, Xiao-Dong Zhu, Lu Lu, Yuan-Yuan Zhang, Yang Bu, Ling-Qun Kong, Zhao-You Tang

Published in: Journal of Hematology & Oncology | Issue 1/2014

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Abstract

Background

Cancer stem cells (CSCs) play a key role in the posthepatectomy recurrence of hepatocellular carcinoma (HCC). CD133+ HCC cells exhibit liver CSC–like properties, and CSC differentiation–inducing therapy may lead these cells to lose their self-renewal ability and may induce terminal differentiation, which may in turn allow their malignant potential to be controlled. Because arsenic trioxide (As2O3) increases remission rates and prolongs survival among patients with acute promyelocytic leukemia by inducing differentiation and apoptosis of leukemic cells, we hypothesized that As2O3 might also inhibit HCC recurrence and prolong survival time after hepatectomy by inducing differentiation of HCC CSCs.

Methods

We evaluated the As2O3 induced differentiation of human HCC CSCs and its mechanism in vitro, and we investigated the effects of treatment with As2O3 on recurrence rates and median survival in a mouse xenograft model.

Results

We found that As2O3 induced HCC CSC differentiation by down-regulating the expression of CD133 and some stemness genes, thus inhibiting the cells’ self-renewal ability and tumorigenic capacity without inhibiting their proliferation in vitro. In vivo experiments indicated that As2O3 decreased recurrence rates after radical resection and prolonged survival in a mouse model. As2O3, which shows no apparent toxicity, may induce HCC CSC differentiation by down-regulating the expression of GLI1.

Conclusions

We found that As2O3 induced HCC CSC differentiation, inhibited recurrence, and prolonged survival after hepatectomy by targeting GLI1 expression. Our results suggest that the clinical safety and utility of As2O3 should be further evaluated.
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Metadata
Title
Arsenic trioxide induces differentiation of CD133+ hepatocellular carcinoma cells and prolongs posthepatectomy survival by targeting GLI1 expression in a mouse model
Authors
Ke-Zhi Zhang
Qiang-Bo Zhang
Quan-Bao Zhang
Hui-Chuan Sun
Jian-Yang Ao
Zong-Tao Chai
Xiao-Dong Zhu
Lu Lu
Yuan-Yuan Zhang
Yang Bu
Ling-Qun Kong
Zhao-You Tang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2014
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-7-28

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