Author:
Zhang Zhongkai,Ha Sang Hoon,Moon Young Jae,Hussein Usama Khamis,Song Yiping,Kim Kyoung Min,Park See-Hyoung,Park Ho Sung,Park Byung-Hyun,Ahn Ae-Ri,Lee Sang-A,Ahn Su Jin,Kim Jung Ryul,Jang Kyu Yun
Abstract
Abstract
Background
SIRT6 has diverse roles in cells, and the role of SIRT6 in tumorigenesis is controversial. Considering the role of SIRT6 as an inducer of DNA damage repair, it might be involved in resistance to anti-cancer therapy.
Methods
We evaluated the prognostic significance of SIRT6 in 37 osteosarcomas and investigated the therapeutic efficacy of SIRT6 on the anticancer effects of doxorubicin, olaparib, and ATM inhibitor.
Results
Immunohistochemical expression of SIRT6 was significantly associated with shorter overall survival and relapse-free survival of osteosarcoma patients, especially in patients who received adjuvant chemotherapy. In U2OS and KHOS/NP osteosarcoma cells, knock-down of SIRT6 significantly potentiated apoptotic effects of doxorubicin and SIRT6 overexpression induced resistance to doxorubicin. Moreover, SIRT6 induced the DNA damage repair pathway and SIRT6-mediated resistance to doxorubicin was attenuated by blocking the DNA damage repair pathway with olaparib and ATM inhibitor.
Conclusions
This study suggests that suppression of SIRT6 in combination with doxorubicin might be an effective modality in the treatment of osteosarcoma patients, especially for osteosarcomas with shorter survival with high expression of SIRT6.
Funder
Ministry of Science ICT and Future Planning
Publisher
Springer Science and Business Media LLC
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