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- Title
The PARP inhibitor olaparib potentiates the effect of the DNA damaging agent doxorubicin in osteosarcoma.
- Authors
Park, Hye Jeong; Bae, Jun Sang; Kim, Kyoung Min; Moon, Young Jae; Park, See-Hyoung; Ha, Sang Hoon; Hussein, Usama Khamis; Zhang, Zhongkai; Park, Ho Sung; Park, Byung-Hyun; Moon, Woo Sung; Kim, Jung Ryul; Jang, Kyu Yun
- 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.
- Subjects
OSTEOSARCOMA; BONE cancer; POLY ADP ribose; DNA damage; DOXORUBICIN; OLAPARIB
- Publication
Journal of Experimental & Clinical Cancer Research (17569966), 2018, Vol 37, Issue 1, pN.PAG
- ISSN
1756-9966
- Publication type
Article
- DOI
10.1186/s13046-018-0772-9