Abstract:
:Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and a key element in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Moreover, it is a negative regulator of autophagy and acts as a central regulator in cell growth. For the treatment of cancer, mTOR is a novel and validated therapeutic target. Previous studies have shown that Akt is frequently activated in nasopharyngeal carcinoma (NPC) tissues; thus, the inhibition of mTOR may be a treatment strategy for this tumor type. To evaluate the effect of the mTOR inhibitor RAD001 on NPC cell lines, we performed 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assays, lactate dehydrogenase (LDH) assays, western blotting and flow cytometry to evaluate the mechanisms of cell death. The growth of both CNE-1 and HONE-1 cells was inhibited in a time- and dose-dependent manner. CNE-1 was more sensitive, with a 50% growth inhibition (GI50) of 30.0±1.0 µM compared to HONE-1, cells which had a GI50 of 56.9±13.1 µM. RAD001 induced apoptosis and autophagy in both cell lines. RAD001 induced a significant increase in growth inhibition in the two cell lines when used in combination with the autophagy inhibitor, 3-methyladenine; however, the percentages of apoptotic cells decreased when RAD001 was combined with the caspase inhibitor, z-VAD-fmk. In conclusion, the main mechanism of the mTOR inhibitor RAD001 in these two NPC cells was apoptotic, not autophagic cell death. The combination of RAD001 with autophagy inhibitors may be a useful therapeutic strategy for nasopharyngeal carcinoma.
journal_name
Int J Mol Medjournal_title
International journal of molecular medicineauthors
Cai Y,Xia Q,Su Q,Luo R,Sun Y,Shi Y,Jiang Wdoi
10.3892/ijmm.2013.1282subject
Has Abstractpub_date
2013-04-01 00:00:00pages
904-12issue
4eissn
1107-3756issn
1791-244Xjournal_volume
31pub_type
杂志文章abstract::The human immunodeficiency virus type 1 (HIV-1) epidemic in Brazil is spreading to small municipalities as well as the innermost parts of the country and scarce information has been reported on the frequency of HIV-1 resistance-associated mutations in these areas. To determine the frequency and diversity of the HIV-1 ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2010-10-01 00:00:00
abstract::Reactive oxygen species (ROS), generated either extracellularly or intracellularly through ligand-receptor interactions, can function as signal transduction molecules to activate the chemotactic cytokine interleukin-8 (IL-8) and the cell surface adhesion protein, intercellular adhesion molecule-1 (ICAM-1; CD54). Toget...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.4.3.223
更新日期:1999-09-01 00:00:00
abstract::Guettarda speciosa Linn. (G. speciosa, Rubiaceae) has been used as a traditional medicinal plant in Asia for the treatment of various inflammatory conditions, including cough, fever and maternal postpartum infection. However, the mechanisms underlying the anti‑inflammatory action of G. speciosa extracts have remained ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3377
更新日期:2018-03-01 00:00:00
abstract::Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, t...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2778
更新日期:2016-12-01 00:00:00
abstract::microRNAs (miRNAs) are important regulators of gene expression during tumorigenesis. The downregulation of microRNA-9 (miR-9) has been reported in ovarian serous carcinoma (OSC), indicating a role for miR-9 in this type of cancer. In this study, we investigated the biological significance of miR-9 in OSC in vitro. Usi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1400
更新日期:2013-08-01 00:00:00
abstract::The aim of this study was to identify key genes associated with coronary artery disease (CAD) and to explore the related signaling pathways. Gene expression profiles of 110 CAD and 112 non-CAD, healthy patients [CAD index (CADi) >23 and =0, respectively] were downloaded from the Gene Expression Omnibus (GEO) database ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.1817
更新日期:2014-09-01 00:00:00
abstract::Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available worldwide. We investigated the effect of Shoyu polysaccharides (SPS) prepared from soy sauce on the intestinal immune system of mice. SPS enhanced the production of immunoglobulin A (IgA) from Peyer's patch cells in vitro, and its oral ad...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2008-08-01 00:00:00
abstract::Free radicals derived from the reaction of iron and oxygen are thought to be one of the causes of tissue injury. In order to identify whether oxygen concentrations are an important factor in iron-mediated damage to cells, cytotoxic effects of Fe(3+)-NTA on human fibroblasts (KMST-6 line) were studied under the conditi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2001-03-01 00:00:00
abstract::The aim of the present study was to examine the protective effect of caveolin‑1 (Cav‑1) in the penehyclidine hydrochloride (PHC)‑based inhibition of lipopolysaccharide (LPS)‑induced acute lung injury (ALI) in vivo and in vitro, in addition to the potential underlying mechanisms. In vivo, an ALI rat model was establish...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4117
更新日期:2019-05-01 00:00:00
abstract::The adaptive response of skeletal muscle fibres depends on a variety of biological factors including loading conditions and neuromuscular activity. An extreme type of atrophy-inducing change in contractile activity is represented by the physical disconnection between the motor nerve and its respective fibre unit. Sinc...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract::Exposure of the skin to ultraviolet (UV) radiation causes extracellular matrix (ECM) collapse in the dermis, owing to an increase in matrix metalloproteinase (MMP) production in both the epidermis and dermis, and a decrease in type I collagen expression in the dermis. Recently, black rice (Oryza sativa L.) was reporte...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2018.3508
更新日期:2018-05-01 00:00:00
abstract::Selenium reportedly contribute to the modulation process of protein phosphorylation to regulate various cellular functions including growth, differentiation, proliferation and development. The aim of this study was to investigate whether selenium and Selenoprotein M (SelM) affects the mechanism of Alzheimer's disease....
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm_00000211
更新日期:2009-07-01 00:00:00
abstract::The prognosis of patients suffering from glioblastoma [also referred to as glioblastoma multiforme (GBM)] is dismal despite multimodal therapy. Chemotherapy with temozolomide may suppress tumor growth for a certain period of time (a few months); however, invariable tumor recurrence suggests that glioblastoma initiatin...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2017.3124
更新日期:2017-11-01 00:00:00
abstract::Heparin/heparan sulfate interacting protein (HIP) was initially identified as an adhesion molecule from a human uterine epithelial cell line. It was previously demonstrated that HIP was upregulated in human colorectal cancer. However, its expression was significantly lower in Dukes' D samples compared to earlier Dukes...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
abstract::Dietary fat is an important factor involved in the pathogenesis of inflammatory bowel disease (IBD). It remains unclear how n-3 and n-6 fatty acids modulate intestinal inflammation. In this study, we investigated the effects of n-3 and n-6 fatty acid-rich diets on trinitrobenzene sulfonic acid (TNBS)-induced enteritis...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2003-11-01 00:00:00
abstract::Epidemiological studies have indicated that increased consumption of cruciferous vegetables is associated with a statistically significant reduction in the risk for cancers. The major bioactive agent in these vegetables is a class of sulfur-containing glycosides called glucosinolates. Isothiocyanates, derivatives of g...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-03-01 00:00:00
abstract::Apelin, the endogenous ligand of APJ which is a member of G protein-coupled receptors, has been shown to be expressed in a variety of tissues in vivo and to exert significant biological effects. Studies have indicated that the apelin/APJ system is involved in the regulation of a variety of physiological functions and ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:10.3892/ijmm.2016.2544
更新日期:2016-05-01 00:00:00
abstract::Graves' ophthalmopathy (GO) is considered to be an organ-specific autoimmune disease. However, the pathogenesis of GO is incompletely understood at the present time. To clarify the immunological differences between newly diagnosed GO and Graves' disease (GD) without ophthalmopathy or healthy controls (HC), we examined...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-05-01 00:00:00
abstract::Long non‑coding RNAs (lncRNAs) have been increasingly recognized as important immune checkpoints involved in the pathogenesis of autoimmune diseases. However, the exact role of lncRNAs in Hashimoto's thyroiditis (HT) has been rarely studied. The aim of the present study was to investigate the role of lncRNAs and the p...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2020.4755
更新日期:2020-12-01 00:00:00
abstract::Cerebral aneurysms and arteriovenous malformations (AVM) are a common cause of stroke and cerebral hemorrage. Both are often discovered when they rupture, causing subarachnoid hemorrhage (SAH). SAH-induced vasospasm is mediated by enhanced vasoconstriction due to endothelin-1 (ET-1). We investigated whether endothelia...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2006-11-01 00:00:00
abstract::Receptor-mediated gene delivery is an attractive method for gene transfer in vitro and shows promise for in vivo gene therapy applications. In the current study, we have selected the cytokine interleukin-2 (IL-2) gene to explore the feasibility of receptor-mediated gene transfer into human hepatocellular carcinoma Hep...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.3.6.601
更新日期:1999-06-01 00:00:00
abstract::An effective therapeutic strategy for suppressing liver fibrosis development should improve the overall prognosis of patients with chronic liver diseases. Despite efforts to develop anti-fibrotic agents, no drugs have yet been approved as anti-fibrotic treatments for humans. An alternative strategy may be to employ a ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2011.658
更新日期:2011-07-01 00:00:00
abstract::We have previously reported comparative genomics analyses on FGF3, FGF4, FGF6, FGF7, FGF8, FGF10, FGF11, FGF17, FGF18, FGF19, FGF20, FGF22 and FGF23 genes. Here, we performed comparative genomics analyses on FGF1, FGF2, FGF5, FGF9, FGF12, FGF13, FGF14, FGF16 and FGF21 genes, and further characterized the FGF16 gene. C...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2005-11-01 00:00:00
abstract::A dietary deprivation in long-chain polyunsaturated omega3 fatty acids initiated in 7-week old normal rats provokes within 3 to 7 months the appearance of several features of the metabolic syndrome. Likewise, within 2 to 4-5 weeks exposure to a flaxseed oil-enriched diet, these anomalies are rapidly corrected. The pre...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm_00000304
更新日期:2009-12-01 00:00:00
abstract::Recent studies have suggested that calcium‑activated potassium channel (KCa) agonists increase the proportion of mouse embryonic stem cell‑derived cardiomyocytes and promote the differentiation of pacemaker cells. In the present study, it was hypothesized that adipose‑derived stem cells (ADSCs) can differentiate into ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2019.4374
更新日期:2019-12-01 00:00:00
abstract::The number of regulatory T cells (Treg cells) and the expression of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1; also known as CD39) and 5'-ectonucleotidase (NT5E; also known as CD73) on the Treg cell surface are increased during sepsis. In this study, to determine the factors leading to the high expressi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2016.2679
更新日期:2016-09-01 00:00:00
abstract::Idiopathic cardiomyopathy is reviewed from molecular standpoint. About a half of all patients with hypertrophic cardiomyopathy show intra-familial occurrence. In familial hypertrophic cardiomyopathy, nine gene abnormalities have been discovered in the sarcomere, i.e. the genes of beta cardiac myosin heavy chain, cardi...
journal_title:International journal of molecular medicine
pub_type: 杂志文章,评审
doi:
更新日期:2003-01-01 00:00:00
abstract::Metastasis is a hallmark of malignant neuroblastoma and is the main reason for therapeutic failure and recurrence of the tumor. The CXC chemokine receptor-4 (CXCR4), a Gi protein-coupled receptor for the ligand CXCL12/stromal cell-derived factor-1α (SDF-1α), is expressed in various types of tumor. This receptor mediat...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2014.2032
更新日期:2015-02-01 00:00:00
abstract::We report the identification of a cDNA that encodes a putative protein of 94 amino acids and expected molecular weight of 10.7 kDa, the C-terminal half of which is identical to that of PEP19, a small, brain-specific protein involved in Ca++/calmodulin signaling. The novel rat-specific protein, tentatively named long P...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:
更新日期:2007-03-01 00:00:00
abstract::The present study aimed to analyze the responses to autophagy in osteoarthritis (OA) and aging chondrocytes in order to elucidate the role of autophagy in the pathogenesis of OA. We used multiple assays to confirm that autophagic activity was downregulated in chondrocytes of aged articular cartilage. Surprisingly, we ...
journal_title:International journal of molecular medicine
pub_type: 杂志文章
doi:10.3892/ijmm.2013.1520
更新日期:2013-12-01 00:00:00