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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

The PARP inhibitor olaparib potentiates the effect of the DNA damaging agent doxorubicin in osteosarcoma

Authors: Hye Jeong Park, Jun Sang Bae, Kyoung Min Kim, Young Jae Moon, See-Hyoung Park, Sang Hoon Ha, Usama Khamis Hussein, Zhongkai Zhang, Ho Sung Park, Byung-Hyun Park, Woo Sung Moon, Jung Ryul Kim, Kyu Yun Jang

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

PARP1 facilitates the recovery of DNA-damaged cells by recruiting DNA damage response molecules such as γH2AX and BRCA1/2, and plays a role in resistance to antitumor therapies. Therefore, PARP inhibition being evaluated as an anti-cancer therapy. However, there are limited studies regrading PARP inhibition in osteosarcoma.

Methods

We evaluated the expression of DNA damage response molecules in 35 human osteosarcomas and investigated the effects of co-treatment of the PARP inhibitor, olaparib, and doxorubicin in osteosarcoma cells.

Results

The expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 were significantly associated with shorter survival of osteosarcoma patients. In osteosarcoma cells, knock-down of PARP1 and treatment of olaparib significantly inhibited proliferation of cells and induced apoptosis. Moreover, the anti-tumor effect was more significant with co-treatment of olaparib and doxorubicin in vitro and in vivo.

Conclusions

This study suggests that combined use of a PARP inhibitor with doxorubicin, a DNA damaging agent, might be effective in the treatment of osteosarcoma patients, especially in the poor-prognostic subgroups of osteosarcoma expressing PARP1, γH2AX, or BRCA1/2.
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Metadata
Title
The PARP inhibitor olaparib potentiates the effect of the DNA damaging agent doxorubicin in osteosarcoma
Authors
Hye Jeong Park
Jun Sang Bae
Kyoung Min Kim
Young Jae Moon
See-Hyoung Park
Sang Hoon Ha
Usama Khamis Hussein
Zhongkai Zhang
Ho Sung Park
Byung-Hyun Park
Woo Sung Moon
Jung Ryul Kim
Kyu Yun Jang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0772-9

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