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Effects of the combination of As2O3 and AZT on proliferation inhibition and apoptosis induction of hepatoma HepG2 cells following silencing of Egr-1

Authors Zhao C, Wang M, Liu Y, Liang YJ, Han L, Chen C

Received 25 October 2017

Accepted for publication 4 February 2018

Published 1 June 2018 Volume 2018:11 Pages 3293—3301

DOI https://doi.org/10.2147/OTT.S155169

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ashok Kumar Pandurangan

Peer reviewer comments 2

Editor who approved publication: Professor Jianmin Xu


Chuan Zhao,1,* Mei Wang,1,* Yu Liu,1 Yongjuan Liang,1 Li Han,2 Che Chen1

1Department of Clinical Laboratory Diagnostics and Molecular Biology, Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu, China; 2Emergency Research Institution, Lanzhou University Second Hospital, Lanzhou, Gansu, China

*These authors contributed equally to this work

Context: Previous studies have demonstrated that 3´-azido-3´-deoxythymidine (AZT) and arsenic trioxide (As2O3), traditional chemotherapy agents, can synergically inhibit the growth of hepatocellular carcinoma cells. However, the molecular mechanisms underlying As2O3 and AZT anti-hepatoma activity are unknown.
Objective: This study aimed to investigate the role of early growth response protein 1 (Egr-1) in the process of As2O3 combined with AZT inhibiting proliferation and inducing apoptosis of human hepatocellular carcinoma HepG2 cells, and explore the possible mechanism.
Materials and methods: The expression of Egr-1 was silenced using siRNA, and then HepG2 cells were treated with As2O3 (2 μM) and AZT (20 μM). The rates of cell inhibition and apoptosis were determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) method and flow cytometry, respectively. The mRNA and protein expression of p53, caspase-3, and Egr-1 were detected by real-time quantitative polymerase chain reaction and Western blotting, respectively.
Results: The inhibitory rate of As2O3 (2 μM) combined with AZT (20 μM) on proliferation of HepG2 cells was significantly higher than that of As2O3 alone. The combination index (CI) values were 0.2
Conclusion: The present results show that AZT could increase the sensitization of As2O3 for inhibiting proliferation and promoting apoptosis of HepG2 cells through regulating the expression of Egr-1, which may control the expression of p53 and caspase-3.

Keywords: HepG2, As2O3, AZT, Egr-1, proliferation, apoptosis

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