详情页 - 广东省中医院知识库

当前位置：首页 > 详情页

Combination BET Family Protein and HDAC Inhibition Synergistically Elicits Chondrosarcoma Cell Apoptosis Through RAD51-Related DNA Damage Repair.

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]Institute of Orthopedic Diseases and Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong, People’s Republic of China [2]School of Life Science, Xiamen University, Xiamen, Fujian 361005, People’s Republic of China [3]Department of Orthopedics, The Third Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, People’s Republic of China [4]IAN WO Medical Center, Macao Special Administrative Region, People’s Republic of China

出处：

DOI：

ISSN：

关键词： chondrosarcoma JQ1 HDAC apoptosis RAD51 DNA repair

摘要：

Chondrosarcoma is the second-most common type of bone tumor and has inherent resistance to conventional chemotherapy. Present study aimed to explore the therapeutic effect and specific mechanism(s) of combination BET family protein and HDAC inhibition in chondrosarcoma. Two chondrosarcoma cells were treated with BET family protein inhibitor (JQ1) and histone deacetylase inhibitors (HDACIs) (vorinostat/SAHA or panobinostat/PANO) separately or in combination; then, the cell viability was determined by Cell Counting Kit-8 (CCK-8) assay, and the combination index (CI) was calculated by the Chou method; cell proliferation was evaluated by 5-ethynyl-2'-deoxyuridine (EdU) incorporation and colony formation assay; cell apoptosis and reactive oxygen species (ROS) level were determined by flow cytometry; protein expressions of caspase-3, Bcl-XL, Bcl-2, γ-H2AX, and RAD51 were examined by Immunoblotting; DNA damage was determined by comet assay; RAD51 and γ-H2AX foci were observed by immunofluorescence. Combined treatment with JQ1 and SAHA or PANO synergistically suppressed the growth and colony formation ability of the chondrosarcoma cells. Combined BET and HDAC inhibition also significantly elevated the ROS level, followed by the activation of cleaved-caspase-3, and the downregulation of Bcl-2 and Bcl-XL. Mechanistically, combination treatment with JQ1 and SAHA caused numerous DNA double-strand breaks (DSBs), as evidenced by the comet assay. The increase in γ-H2AX expression and foci formation also consistently indicated the accumulation of DNA damage upon cotreatment with JQ1 and SAHA. Furthermore, RAD51, a key protein of homologous recombination (HR) DNA repair, was found to be profoundly suppressed. In contrast, ectopic expression of RAD51 partially rescued SW 1353 cell apoptosis by inhibiting the expression of cleaved-caspase-3. Taken together, our results disclose that BET and HDAC inhibition synergistically inhibit cell growth and induce cell apoptosis through a mechanism that involves the suppression of RAD51-related HR DNA repair in chondrosarcoma cells. © 2020 Huan et al.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2019]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

最新[2025]版：

大类 | 4 区医学

小类 | 4 区肿瘤学

第一作者：

第一作者机构： [1]Institute of Orthopedic Diseases and Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou 510630, Guangdong, People’s Republic of China

共同第一作者：

通讯作者：

推荐引用方式(GB/T 7714)：

APA：

MLA：

相关文献

[1]The BET Bromodomain Inhibitor JQ1 Suppresses Chondrosarcoma Cell Growth via Regulation of YAP/p21/c-Myc Signaling. [2]Isoorientin triggers apoptosis of hepatoblastoma by inducing DNA double-strand breaks and suppressing homologous recombination repair [3]DNA repair mechanisms in embryonic stem cells [4]Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF-1/SOX9 Axis. [5]SUMOylation of Nuclear gamma-Actin by SUMO2 supports DNA Damage Repair against Myocardial Ischemia-Reperfusion Injury [6]Genetic variants in the nucleotide excision repair pathway genes and gastric cancer susceptibility in a southern Chinese population. [7]XRCC1 gene polymorphisms and risk of neuroblastoma in Chinese children. [8]HELQ as a DNA helicase: Its novel role in normal cell function and tumorigenesis (Review) [9]Functional Polymorphisms in hOGG1 Gene and Neuroblastoma Risk in Chinese Children. [10]Relevance of XPD polymorphisms to neuroblastoma risk in Chinese children: a four-center case-control study.