Abstract:
Background:Bromodomain and extra-terminal domain inhibitors like JQ1 have proved to be promising epigenetic agents for the treatment of malignant ovarian carcinoma. However, the resistance of ovarian cancer cells to BET inhibitors has not been elucidated. In this study, we investigated the potential mechanisms underlying the resistance of ovarian cancer cell lines to the BET inhibitor JQ1. Materials and methods:We evaluated the apoptotic and proliferative response of four ovarian cancer cell lines to JQ1. The cell lines were designated as resistant (A2780 and HO-8910) and sensitive groups (SKOV-3 and HEY). Further experiments detected the different levels of JQ1-induced autophagy. Anti-tumour effect of the combination of JQ1 and autophagy inhibitors was tested both in vitro and in vivo. Results:In the JQ1-sensitive group, JQ1 effectively inhibited proliferation and apoptosis in a concentration-dependent manner. Conversely, JQ1 showed modest inhibition of proliferation and negligible apoptosis in the resistant group. We detected increased LC3-II lipidation, autophagosome formation, upregulation of Beclin-1 and ATG5, and downregulation of P62/SQSTM1 in the resistant group. Inhibition of JQ1-induced autophagy by pharmacologic inhibitors 3-MA and CQ enhanced the inhibition of proliferation and significantly increased the apoptosis in the JQ1-resistant group, which was also verified by in vivo experiments, indicating that JQ1-induced autophagy played a cytoprotective role. Inactivation of Akt (Ser473)/mTOR(Ser2448) pathway was associated with JQ1-induced autophagy in the resistant group. Overexpression of Akt1 suppressed autophagy and increased the anti-tumour effect of JQ1. Conclusion:These findings revealed that JQ1-induced pro-survival autophagy might be a potential mechanism in the resistance of ovarian cancer cells to BET inhibition by JQ1. Combination of JQ1 and autophagy inhibitors could be an effective therapeutic strategy for overcoming BET inhibitor resistance in ovarian cancer.
journal_name
Onco Targets Therjournal_title
OncoTargets and therapyauthors
Luan W,Pang Y,Li R,Wei X,Jiao X,Shi J,Yu J,Mao H,Liu Pdoi
10.2147/OTT.S220267subject
Has Abstractpub_date
2019-10-03 00:00:00pages
8063-8074issn
1178-6930pii
220267journal_volume
12pub_type
杂志文章abstract:Purpose:Sorafenib has revolutionized treatment of hepatocellular carcinoma (HCC), but its efficacy is limited by drug resistance. Autophagy is the process by which cellular components are transported to lysosomes for degradation, which promotes energy production and production of macromolecular precursors. Studies have...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S247655
更新日期:2020-04-28 00:00:00
abstract:Background:Malignant glioma is the second leading cause of cancer-related death worldwide, and is known to exhibit a high degree of heterogeneity in its deregulation of different oncogenic pathways. The molecular subclasses of human glioma are not well known. Thus, it is crucial to identify vital oncogenic pathways in ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S139243
更新日期:2017-11-15 00:00:00
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:Purpose:Here, we investigated the involvement of the miR-188-5p/inhibitor of the DNA binding 4 (ID4) axis in retinoblastoma (Rb). Patients and methods:We included 35 Rb tissues and the corresponding adjacent normal tissues. RT-qPCR, Western blot, lentivirus transfection, measurement of cell migration in vitro, and chi...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S229739
更新日期:2019-11-27 00:00:00
abstract:Background:Investigating the roles of lncRNA prostate cancer-associated transcript 6 (PCAT6) in modulating the growth and aggressiveness of non-small-cell lung carcinoma (NSCLC) cell. Method:The levels of PCAT6 in NSCLC tissues and cell lines were determined by quantitative real-time PCR assay. MTT as well as colony f...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S178597
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND AND PURPOSE:Vandetanib is a promising anticancer targeted agent for treating advanced carcinomas, such as non-small-cell lung cancer, small-cell lung cancer, breast cancer, malignant glioma, hepatocellular cancer, and unresectable, locally advanced, or metastatic medullary thyroid cancer. However, diarrhea i...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S96830
更新日期:2016-06-20 00:00:00
abstract:PURPOSE:To evaluate whether the addition of two biological markers (MYC and BCL-2 protein overexpression) improves the stratification of high-risk patients with diffuse large B-cell lymphoma (DLBCL). METHOD:Seven risk factors were identified at diagnosis, and a maximum of 7 points were assigned to each patient. The pa...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S86093
更新日期:2015-09-18 00:00:00
abstract:Purpose:Pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) is associated with favourable outcomes of patients with triple-negative breast cancer (TNBC). However, a proportion of TNBC patients with the residual disease do not relapse and achieve long-term survival. The aim of this study was to ident...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S256818
更新日期:2020-07-03 00:00:00
abstract:Introduction:Multiple myeloma (MM) remains an incurable disease, and patient survival requires a better understanding of this malignancy's molecular aspects. Heparanase (HPSE) is highly expressed in aggressive MM cells and related to tumor growth, metastasis, and bortezomib (BTZ) resistance. Thus, targeting HPSE seems ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S286751
更新日期:2021-01-15 00:00:00
abstract::Targeted radioimmunotherapy in non-Hodgkin's B-cell lymphoma (NHL) offers an efficacious therapy and minimal toxicity compared to conventional chemotherapy. Iodine 131 tositumomab ((131)I-TST) is a murine monoclonal antibody against the CD20 cell surface protein and is directly covalently conjugated to (131)I, a radio...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/ott.s4456
更新日期:2009-02-18 00:00:00
abstract::Background and aims: HOXD antisense growth-associated long noncoding RNA (HOXD-AS1) was reported to be upregulated in various cancers, such as gastric cancer, hepatocellular carcinoma, colorectal cancer, and glioma. Here, we conducted a meta-analysis and The Cancer Genome Atlas data review to investigate the clinicopa...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S184303
更新日期:2018-11-05 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::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: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::Malignant pericardial effusion (MPCE) is a common complication of advanced malignant tumors, and interferes severely with patient prognosis and quality of life. The standard treatment for this complication is intracavitary perfusion of chemotherapeutic drugs, which is limited by unsatisfactory therapeutic effects and ...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S90145
更新日期:2015-10-01 00:00:00
abstract::In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K) pathway. The PI3K pathway seems to play an...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S34641
更新日期:2014-02-21 00:00:00
abstract:Background:The neutrophil-lymphocyte ratio (NLR), a biomarker for systematic inflammation, has been recently identified as a prognostic factor for various types of both solid and hematologic malignancies. Our study presented here was the first meta-analysis assessing the prognostic role of NLR in multiple myeloma (MM)....
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S153146
更新日期:2018-01-23 00:00:00
abstract:Background:Hepatocellular carcinoma is a common malignant cancer and the second most common cause of cancer-related deaths worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been increasingly reported to be involved in tumorigenesis and/or tumor progression. However, limited data are available regarding ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S219429
更新日期:2019-09-23 00:00:00
abstract:BACKGROUND:Forkhead box Q1 (FOXQ1, also known as HFH1), a member of the forkhead transcription factor family, has been demonstrated to be overexpressed in multiple tumors and is thought to be an indicator of poor clinical outcomes. METHODS:A meta-analysis using qualified relevant literature was performed to evaluate t...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S130905
更新日期:2017-03-23 00:00:00
abstract:Background:Despite the breadth of understanding the noncoding RNAs' function in molecular biology, their functional roles in hepatocellular carcinoma (HCC) is poorly understood. In this study, we investigated the effect of hepatitis C virus (HCV) core upon the expression of noncoding RNAs. Methods:The lncRNAs, mRNAs, ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S149254
更新日期:2018-03-02 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::Angiogenesis plays an essential role in the development of most solid tumors by delivering nutrients and oxygen to the tumor. Therefore, anti-angiogenic therapy, particularly anti-VEGF and anti-VEGF receptor (VEGFR) therapy, has been a popular strategy to treat cancer. However, anti-angiogenic therapy does not signifi...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S276150
更新日期:2020-11-24 00:00:00
abstract:AIM:To investigate the significance of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER3 expression on survival outcomes in Chinese gastric cancer patients. MATERIALS AND METHODS:Formalin-fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at Sh...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S70922
更新日期:2014-12-16 00:00:00
abstract:BACKGROUND:According to the relevant reports, TIMP-2 polymorphism might be associated with the susceptibility to gastric cancer. Owing to the inconclusive results from the published studies based on the association between TIMP-2 single nucleotide polymorphisms (SNPs) and gastric cancer susceptibility, a meta-analysis ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S114113
更新日期:2016-11-03 00:00:00
abstract:BACKGROUND:Recent studies have demonstrated that the clock gene PER1 regulates various tumor-related genes. Abnormal expressions and circadian rhythm alterations of PER1 are closely related to carcinogenesis. However, the dynamic circadian variations of PER1 and tumor-related genes at different stages of carcinogenesis...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S83710
更新日期:2015-06-11 00:00:00
abstract::Lung cancer is the leading cause of cancer-related mortality in both sexes, accounting for over one quarter of cancer deaths. Non-small-cell lung cancer (NSCLC) comprises 85%-90% of lung cancer diagnoses and despite advances in multimodality therapies, 5-year survival rates remain dismal with a median survival for pat...
journal_title:OncoTargets and therapy
pub_type: 杂志文章,评审
doi:10.2147/OTT.S67262
更新日期:2015-04-20 00:00:00
abstract:Background:Chemotherapy remains a major clinical option for the successful treatment of cancer by eliminating fast-growing populations of cancer cells. However, drug resistance causes the failure of antitumor treatment. Increasing evidence suggests that a small subpopulation of cancer cells will enter a "persister stat...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S212465
更新日期:2019-07-08 00:00:00
abstract:Background:Growing evidence suggests that miR-150 plays an inhibitory role in various types of cancer. However, the function and underlying mechanisms of miR-150 in triple-negative breast cancer (TNBC) remain unknown. Patients and methods:miR-150 expression was detected by qRT-PCR and ISH in TNBC tumor and adjacent no...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S161996
更新日期:2018-04-24 00:00:00
abstract:Background/aim:Urothelial bladder cancer arises from the accumulation of multiple epigenetic and genetic changes. We aimed to investigate the specificity and sensitivity of gene-specific promoter methylation of CDH1 and p14ARF genes in the early diagnosis of bladder cancer and compare those with other diagnostic tests ...
journal_title:OncoTargets and therapy
pub_type: 杂志文章
doi:10.2147/OTT.S158259
更新日期:2018-07-19 00:00:00
abstract::The prevalence of cancer remains high. With the improvement of diagnosis and treatment level and the increase of cancer survivors after treatment, multiple primary tumors are more common than before. The diagnosis and treatment of synchronous multiple primary tumors is more complicated than that of single or metachron...
journal_title:OncoTargets and therapy
pub_type:
doi:10.2147/OTT.S200625
更新日期:2019-04-02 00:00:00