期刊
CELLULAR ONCOLOGY
卷 43, 期 3, 页码 461-475出版社
SPRINGER
DOI: 10.1007/s13402-020-00502-y
关键词
Dp44mT; NDRG2; RORA; Glioma; Proliferation; Apoptosis; IL6; JAK2; STAT3
资金
- National Natural Science Foundation of China [81101917, 81270036, 30901736]
- Plan to Focus on Research and Development from Science and Technology project of Liaoning Province [2017225029]
- Natural Science Foundation of Liaoning Province [20170541022]
- Liaoning BaiQianWan Talents Program [2019-B45]
- Science and Technology Plan Project of Shenyang City [18-014-4-11]
- Fund for Scientific Research of The First Hospital of China Medical University [FHCMU- FSR]
- Shanghai Sailing Program [19YF1439000]
Purpose The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown. Methods Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays. Results We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling. Conclusions Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
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