Abstract:
:We studied Akt inhibition using SC66 in a NOD-SCID xenograft mouse model and a panel of eight ovarian cancer cell lines. Elevated phospho-Akt levels in cancerous tissue were associated with short progression-free survival and overall survival. Cell sensitivity to SC66 was inversely correlated with phospho-Akt and COL11A1 expression levels, as well as resistance to cisplatin or paclitaxel. SC66 inhibited phosphorylation of Akt and its downstream effectors 4EBP1 and p70S6 kinase. SC66 also attenuated expression of TWIST1 and Mcl-1, factors important in cell invasiveness and anti-apoptosis, respectively. SC66-sensitized chemoresistant cells to cisplatin and paclitaxel treatment, and promoted apoptosis. In addition, SC66 inhibited COL11A1 expression via decreased binding of CCAAT/enhancer-binding protein beta (c/EBPβ), reducing chemoresistance and decreasing binding of nuclear transcription factor Y (NF-YA) to COL11A1. A mouse xenograft experiment demonstrated that SC66 treatment caused a reduction in tumor formation and enhanced the therapeutic efficacy of cisplatin. This study demonstrates the role of Akt in ovarian tumor progression and chemoresistance, and supports the application of SC66 as a therapy for ovarian cancer.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Wu YH,Huang YF,Chen CC,Chou CYdoi
10.1038/s41419-019-1555-8subject
Has Abstractpub_date
2019-04-11 00:00:00pages
322issue
4issn
2041-4889pii
10.1038/s41419-019-1555-8journal_volume
10pub_type
杂志文章abstract::Ionizing radiation (IR) response has been extensively investigated in BMSCs with an increasing consensus that this type of cells showed relative radiosensitivity in vitro analysis. However, the underlying mechanism of IR-induced injury of BMSCs has not been elucidated. In current study, the regulatory role of miR-22/R...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1373-z
更新日期:2019-03-07 00:00:00
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journal_title:Cell death & disease
pub_type: 已发布勘误
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journal_title:Cell death & disease
pub_type: 杂志文章
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journal_title:Cell death & disease
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journal_title:Cell death & disease
pub_type: 杂志文章
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abstract::Chemotherapy is a standard treatment for non-small-cell lung cancer (NSCLC). However, the dose-limiting toxicity of drugs and the development of chemoresistance are major clinical challenges to successful management of NSCLC. Asian traditional medicine is gaining global attention as a non-toxic alternative to chemothe...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0277-7
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abstract::The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients' survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) sp...
journal_title:Cell death & disease
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journal_title:Cell death & disease
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doi:10.1038/s41419-017-0188-z
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.519
更新日期:2017-10-12 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2020-03-30 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
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更新日期:2018-12-18 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0400-9
更新日期:2018-03-06 00:00:00
abstract::SHP2 participates in multiple signaling events by mediating T-cell development and function, and regulates cytokine-dependent granulopoiesis. To explore whether and how SHP2 can regulate bone-marrow eosinophil differentiation, we investigate the contribution of SHP2 in the bone-marrow eosinophil development in allergi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.74
更新日期:2016-04-07 00:00:00
abstract::Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacol...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.501
更新日期:2017-10-05 00:00:00
abstract::Cognitive aging is a leading public health concern with the increasing aging population, but there is still lack of specific interventions directed against it. Recent studies have shown that cognitive function is intimately affected by systemic milieu in aging brain, and improvement of systemic environment in aging br...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.316
更新日期:2017-08-10 00:00:00
abstract::Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially of the lead compound Triapine. During the last years, a novel subclass of anticancer thiosemicarbazones has attracted substantial interest ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1102-z
更新日期:2018-10-15 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/cddis.2014.565
更新日期:2015-01-15 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2352-0
更新日期:2020-03-05 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2629-3
更新日期:2020-06-04 00:00:00
abstract::DDX3 is a highly conserved member of ATP-dependent DEAD-box RNA helicases with multiple functions in RNA metabolism and cellular signaling. Here, we describe a novel function for DDX3 in regulating the mitochondrial stress response in the parasitic protozoan Leishmania. We show that genetic inactivation of DDX3 leads ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.315
更新日期:2016-10-13 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.3
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1119-3
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1275-5
更新日期:2019-02-06 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-02759-5
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1915-4
更新日期:2019-10-31 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.51
更新日期:2017-02-23 00:00:00
abstract::Ferroptosis is a novel form of programmed cell death in which the accumulation of intracellular iron promotes lipid peroxidation, leading to cell death. Recently, the induction of autophagy has been suggested during ferroptosis. However, this relationship between autophagy and ferroptosis is still controversial and th...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2064-5
更新日期:2019-10-28 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-2135-7
更新日期:2019-11-26 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.565
更新日期:2017-10-26 00:00:00
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journal_title:Cell death & disease
pub_type: 杂志文章,评审
doi:10.1038/s41419-020-2604-z
更新日期:2020-06-05 00:00:00