Abstract:
Background:Celastrol is a major active component of the thunder god vine (Tripterygium wilfordii) used in traditional Chinese medicine to treat chronic inflammatory and autoimmune diseases. Celastrol inhibits PI3K-Akt-mTOR signaling, which is frequently dysregulated in tumors and critical for tumor-cell proliferation and survival, but the underlying mechanisms are still not fully understood. In the present study, we investigated detailed mechanisms of celastrol inhibition of mTOR signaling in breast cancer cells. Methods:First, we evaluated the effect of celastrol on breast cancer-cell growth using MTT assays. Second, we examined the effects of celastrol on mTOR phosphorylation and expression using Western blot. Furthermore, we investigated the cause of mTOR downregulation by celastrol using immunoprecipitation assays. In addition, we evaluated the effect of celastrol on an MDA-MB231 cell-derived xenograft model. Results:Celastrol suppressed breast cancer cell growth in vitro and in vivo. Celastrol inhibited mTOR phosphorylation and induced mTOR ubiquitination, resulting in its proteasomal degradation. Mechanistically, we found that mTOR is a client of Hsp90-Cdc37 chaperone complex, and celastrol disrupts mTOR interaction with chaperone Hsp90 while promoting mTOR association with cochaperone Cdc37. Conclusion:Our study reveals that celastrol suppresses mTOR signaling, at least in part through regulating its association with chaperones and inducing its ubiquitination.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Li X,Zhu G,Yao X,Wang N,Hu R,Kong Q,Zhou D,Long L,Cai J,Zhou Wdoi
10.2147/OTT.S187315subject
Has Abstractpub_date
2018-12-11 00:00:00pages
8977-8985issn
1178-6930pii
ott-11-8977journal_volume
11pub_type
杂志文章abstract:PURPOSE:We validated the use of expression sequence tags (ESTs) as an effective method of screening for DNA segments that could predict urothelial cell carcinoma and for identifying ESTs with such predictive value. PATIENTS AND METHODS:From 2004 to 2009, eleven patients were enrolled in this study: six with high-grade...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S69239
更新日期:2014-09-30 00:00:00
abstract:Introduction:Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neut...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S153290
更新日期:2018-02-23 00:00:00
abstract::Trastuzumab is a monoclonal antibody directed against the human epidermal growth factor receptor 2 (HER2). HER2 is amplified or overexpressed in about 15% of breast cancers and is associated with aggressive disease. Clinical benefits of trastuzumab have been established in the treatment of both early and metastatic HE...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S27733
更新日期:2013-01-01 00:00:00
abstract:Purpose:To evaluate the association between tertiary Gleason pattern 5 (TGP5) and biochemical recurrence (BCR) in patients with prostate cancer (PCa) with a Gleason score (GS) of 7 after radical prostatectomy (RP). Patients and methods:This retrospective study identified 350 patients who received RP and were graded as...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S218001
更新日期:2019-09-02 00:00:00
abstract:Introduction:Hypoxia and tumor-associated macrophage (TAM) are key regulators in remodeling the microenvironment of esophageal squamous cell carcinoma (ESCC). Hypoxia could stimulate tumor cells to secrete more exosomes and activate TAMs to M2 type. Here, we investigated the function and the underlying mechanism of tum...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S284192
更新日期:2020-11-18 00:00:00
abstract:Purpose:Intraoperative identification of rectal cancer (RC) can be challenging, especially because of fibrosis after treatment with preoperative chemo- and radiotherapy (CRT). Tumor-targeted fluorescence imaging can enhance the contrast between tumor and normal tissue during surgery. Promising targets for RC imaging ar...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S145473
更新日期:2018-03-23 00:00:00
abstract::Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S142598
更新日期:2018-01-19 00:00:00
abstract::Liver cancer is a common malignant disease in China, while the primary hepatic neuroendocrine tumor (PHNET) is extremely rare presented with various manifestations. We herein describe an interesting PHNET case, which was clinically diagnosed as hepatocellular carcinoma (HCC) based on strong clinical evidence and the n...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S236728
更新日期:2020-02-03 00:00:00
abstract:Introduction:Upper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy for which there has not been significant improvement in survival over the past few decades, highlighting the need for optimal multi-modality management. Methods:A non-systematic review of the latest literature was perform...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S225301
更新日期:2020-01-06 00:00:00
abstract:Purpose:This study aimed to investigate the regulatory roles of estrogen receptor beta (ERβ) on gastric cancer (GC) cells, and reveal the potential mechanisms relating to nuclear factor-kappa B (NF-κB) signaling. Methods:GC cell lines SGC7901 and MKN45 were transfected with pEGFP-C1-ERβ to overexpress ERβ, and treated...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,收录出版
doi:10.2147/OTT.S214529
更新日期:2019-11-05 00:00:00
abstract:Background:Addiction to aerobic glycolysis is a common metabolic phenotype in human non-small cell lung cancer (NSCLC). The natural product Sinomenine (Sin) exhibits significant anti-tumor effects in various human cancers. However, the underlying mechanism remains elusive. Methods:The inhibitory effect of Sin on NSCLC...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S243212
更新日期:2020-04-16 00:00:00
abstract::Purpose: LncRNA MIR100HG promotes several types of malignancies, while its involvement in other human diseases is unknown. Patients and methods: Our study included 70 patients with LSCC who were diagnosed and treated in the First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and T...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S202528
更新日期:2019-04-17 00:00:00
abstract:BACKGROUND:Recurrent laryngeal nerve (RLN) invasion in papillary thyroid carcinoma (PTC) is one of the main predictors of poor prognosis. The present study investigated the risk factors for RLN invasion in PTC patients. METHODS:A total of 3,236 patients who received thyroidectomy due to PTC in Thyroid and Parathyroid ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S142799
更新日期:2017-09-11 00:00:00
abstract::Large granular lymphocytic leukemia (LGLL) is a rare lymphoproliferative disorder of transformed natural killer or T-cells attributed to chronic exposure to the proinflammatory cytokine IL-15. Diagnosis of the majority of T-cell LGLL is established by documenting clonal large granular lymphocytes (LGLs) in peripheral ...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S115892
更新日期:2016-12-19 00:00:00
abstract::Activation of the transcription factor, signal transducers and activators of transcription 3 (STAT3), has been linked to the proliferation and migration of a variety of human cancer cells. These actions occur via the upregulation or downregulation of cell survival and tumor suppressor genes, respectively. Importantly,...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S121619
更新日期:2016-12-20 00:00:00
abstract:BACKGROUND:Sunitinib is widely used as first-line treatment for metastatic clear cell renal cancer (MCRC). No reports are known of treatment after sunitinib failure. As irinotecan, cisplatin, and mitomycin-C (IPM) chemotherapy has been reported to influence MCRC after progression on cytokine therapy, we report on the o...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/ott.s3590
更新日期:2008-09-01 00:00:00
abstract::Despite the prominent effects of BCR-ABL tyrosine kinase inhibitors (TKI) therapy in patients with chronic phase-chronic myeloid leukemia (CP-CML) and thus low incidence of blastic transformation, blast phase (BP)-CML remains a major therapeutic challenge in the TKI era. The "gatekeeper" mutation T315I in BCR-ABL1 kin...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S232102
更新日期:2019-12-13 00:00:00
abstract:Purpose:Gastric carcinoma is the second most frequently diagnosed cancer and leading cause of cancer death in China. As a new generation of cancer therapeutic drug, CL-6, a curcumin derivative, shows better bioavailability than curcumin, which has shown anticancer effects in gastric cancer (GC). However, whether CL-6 s...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S196914
更新日期:2019-03-27 00:00:00
abstract::Despite remarkable progress in cancer-drug discovery, the delivery of novel, safe, and sustainably effective products to the clinic has stalled. Using Src as a model, we examine key steps in drug development. The preclinical evidence on the relationship between Src and solid cancer is in sharp contrast with the modest...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S45177
更新日期:2013-06-26 00:00:00
abstract:Background:This study was designed to research the potential function of lncRNA ANRIL in osteosarcoma (OS). Materials and methods:Quantitative real-time PCR, cell counting kit-8, wound healing assay, Transwell assay, flow cytometric analysis, caspase activity analysis, and Western blot were carried out. Results:ANRIL...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S170293
更新日期:2018-08-14 00:00:00
abstract:BACKGROUND:Current cancer treatments have unexpected side effects of which the death of normal cells is one. In some cancers, iron nanoparticles (NPs) can be subjected to diagnosis and passive targeting treatment. Cold atmospheric plasma (CAP) has a proven induction of selective cell death ability. In this study, we ha...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S95644
更新日期:2016-09-28 00:00:00
abstract::This study aimed to investigate the expression and clinical significance of MYC-associated zinc finger protein (MAZ) in pancreatic carcinoma (PC), and the biological functions of MAZ in PC cells. MAZ expression was detected in 57 PC tissues and 41 paired adjacent nontumor tissues by immunohistochemistry. Compared to t...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,收录出版
doi:10.2147/OTT.S124118
更新日期:2016-12-12 00:00:00
abstract:BACKGROUND:Fibroblast growth factor receptor 4 (FGFR4) has been proved to be correlated with progression and prognosis in many cancers. However, the significance of FGFR4 in non-small-cell lung cancer (NSCLC) is still not well elucidated. METHODS:In our experiment, we detected FGFR4 expression in 237 samples of NSCLC ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S81659
更新日期:2015-05-22 00:00:00
abstract:Introduction:Immune-based and antibody-drug conjugate therapies have shown promise in the treatment of patients with small cell lung cancer (SCLC). However, better predictive biomarkers are needed for selection of the appropriate SCLC patients for these advanced therapies and also for evaluation of the efficacy of thes...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S216362
更新日期:2019-11-21 00:00:00
abstract:Background:Tumour growth and development are dependent on many factors including long noncoding RNAs (lncRNAs). However, limited information is available on the involvement of lncRNAs in non-small cell lung cancer (NSCLC) and the molecular mechanisms have not been defined. Here, we examined the expression of small nucl...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S263637
更新日期:2020-11-04 00:00:00
abstract::The incidence rate of breast cancers in People's Republic of China has increased in the last decade, and many cases are responsive to hormone therapies. The third-generation aromatase inhibitor letrozole inhibits estrogen production, and is more efficacious than the estrogen receptor inhibitor tamoxifen. In recent yea...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S81087
更新日期:2016-03-01 00:00:00
abstract::Immune checkpoint inhibitors (ICIs) have transformed the therapeutic strategy and prognosis of advanced non-small cell lung cancer (NSCLC) patients. Nowadays, ICIs as monotherapy or in combination with chemotherapy are the standard of care treatment in advanced NSCLC, and in stage III, durvalumab (a programmed death l...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S259308
更新日期:2020-07-14 00:00:00
abstract:PURPOSE:Subsets of non-small-cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations carry uncommon subtypes. We evaluated the efficacy of first-generation EGFR-tyrosine kinase inhibitors (TKIs; erlotinib, gefitinib, and icotinib) in patients with non-small-cell lung cancer carrying insertions ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S108242
更新日期:2016-07-08 00:00:00
abstract:BACKGROUND:Leucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 was expressed in brain, adipose tissues and skin, where it played roles as a multifunctional cytokine. We postulated that LGI3 may be involved in cytokine network in cancers. AIM:This study ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S138912
更新日期:2017-05-24 00:00:00
abstract::Advanced gastric cancer (AGC) is difficult to treat with poor prognosis. Despite various possible treatments, the median survival time of such patients remains unsatisfactory. Therefore, new therapeutic approaches or combinations need to be further explored. We herein reported a case of a 54-year-old male patient who ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S221436
更新日期:2019-09-19 00:00:00