mTOR inhibitor RAD001 (everolimus) induces apoptotic, not autophagic cell death, in human nasopharyngeal carcinoma cells.

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 Med

authors

Cai Y,Xia Q,Su Q,Luo R,Sun Y,Shi Y,Jiang W

doi

10.3892/ijmm.2013.1282

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

904-12

issue

4

eissn

1107-3756

issn

1791-244X

journal_volume

31

pub_type

杂志文章
  • Frequency and diversity of human immunodeficiency virus type 1 mutations associated with antiretroviral resistance among patients from Southern Brazil failing highly active antiretroviral therapy (HAART).

    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:

    authors: Figueiredo Saad F,Kaminami Morimoto H,Wiechmann SL,Bonametti AM,Ueda LT,Matsuo T,Reiche EM

    更新日期:2010-10-01 00:00:00

  • Oxidant stress regulation of IL-8 and ICAM-1 gene expression: differential activation and binding of the transcription factors AP-1 and NF-kappaB (Review).

    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

    authors: Roebuck KA

    更新日期:1999-09-01 00:00:00

  • Methanol extract of Guettarda speciosa Linn. inhibits the production of inflammatory mediators through the inactivation of Syk and JNK in macrophages.

    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

    authors: Le HTT,Cho YC,Cho S

    更新日期:2018-03-01 00:00:00

  • Paeonol promotes microRNA-126 expression to inhibit monocyte adhesion to ox-LDL-injured vascular endothelial cells and block the activation of the PI3K/Akt/NF-κB pathway.

    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

    authors: Yuan X,Chen J,Dai M

    更新日期:2016-12-01 00:00:00

  • miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1.

    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

    authors: Tang H,Yao L,Tao X,Yu Y,Chen M,Zhang R,Xu C

    更新日期:2013-08-01 00:00:00

  • Identification of key genes and crucial modules associated with coronary artery disease by bioinformatics analysis.

    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

    authors: Zhang X,Cheng X,Liu H,Zheng C,Rao K,Fang Y,Zhou H,Xiong S

    更新日期:2014-09-01 00:00:00

  • Stimulatory effect of Shoyu polysaccharides from soy sauce on the intestinal immune system.

    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:

    authors: Matsushita H,Kobayashi M,Tsukiyama R,Fujimoto M,Suzuki M,Tsuji K,Yamamoto K

    更新日期:2008-08-01 00:00:00

  • Effects of oxygen concentrations on human fibroblasts treated with Fe(3+)-NTA.

    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:

    authors: Pu H,Sakaguchi M,Kondo T,Kondo A,Kawabata T,Namba M

    更新日期:2001-03-01 00:00:00

  • Penehyclidine hydrochloride alleviates lipopolysaccharide‑induced acute lung injury in rats: Potential role of caveolin‑1 expression upregulation.

    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

    authors: Wu X,Kong Q,Xia Z,Zhan L,Duan W,Song X

    更新日期:2019-05-01 00:00:00

  • Early effects of denervation on Ca(2+)-handling proteins in skeletal muscle.

    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:

    authors: Donoghue P,Ribaric S,Moran B,Cebasek V,Erzen I,Ohlendieck K

    更新日期:2004-06-01 00:00:00

  • Black rice (Oryza sativa L.) extract modulates ultraviolet-induced expression of matrix metalloproteinases and procollagen in a skin cell model.

    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

    authors: Han M,Bae JS,Ban JJ,Shin HS,Lee DH,Chung JH

    更新日期:2018-05-01 00:00:00

  • ERK activation induced by selenium treatment significantly downregulates beta/gamma-secretase activity and Tau phosphorylation in the transgenic rat overexpressing human selenoprotein M.

    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

    authors: Yim SY,Chae KR,Shim SB,Hong JT,Park JY,Lee CY,Son HJ,Sheen YY,Hwang DY

    更新日期:2009-07-01 00:00:00

  • MicroRNA-132 induces temozolomide resistance and promotes the formation of cancer stem cell phenotypes by targeting tumor suppressor candidate 3 in glioblastoma.

    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

    authors: Cheng ZX,Yin WB,Wang ZY

    更新日期:2017-11-01 00:00:00

  • The HIP gene encoding a heparin/heparan sulfate interacting protein is mutated in metastatic human colorectal cancer.

    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:

    authors: Wang Y,Tan S,Hooi SC

    更新日期:2003-04-01 00:00:00

  • N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis.

    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:

    authors: Andoh A,Tsujikawa T,Ishizuka I,Araki Y,Sasaki M,Koyama S,Fujiyama Y

    更新日期:2003-11-01 00:00:00

  • Iberin induces cell cycle arrest and apoptosis in human neuroblastoma cells.

    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:

    authors: Jadhav U,Ezhilarasan R,Vaughn SF,Berhow MA,Mohanam S

    更新日期:2007-03-01 00:00:00

  • Apelin/APJ system: A novel therapeutic target for oxidative stress-related inflammatory diseases (Review).

    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

    authors: Zhou Q,Cao J,Chen L

    更新日期:2016-05-01 00:00:00

  • CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy.

    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:

    authors: Xia N,Zhou S,Liang Y,Xiao C,Shen H,Pan H,Deng H,Wang N,Li QQ

    更新日期:2006-05-01 00:00:00

  • Long non‑coding RNA expression profiles identify lncRNA‑XLOC_I2_006631 as a potential novel blood biomarker for Hashimoto's thyroiditis.

    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

    authors: Peng H,Xiong S,Ding X,Tang X,Wang X,Wang L,Liu Y

    更新日期:2020-12-01 00:00:00

  • Endothelial cells from human cerebral aneurysm and arteriovenous malformation release ET-1 in response to vessel rupture.

    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:

    authors: Boscolo E,Pavesi G,Zampieri P,Conconi MT,Calore C,Scienza R,Parnigotto PP,Folin M

    更新日期:2006-11-01 00:00:00

  • Receptor-mediated interleukin-2 gene transfer into human hepatoma cells.

    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

    authors: Junbo H,Li Q,Zaide W,Yunde H

    更新日期:1999-06-01 00:00:00

  • Cocktail therapy with a combination of interferon, ribavirin and angiotensin-II type 1 receptor blocker attenuates murine liver fibrosis development.

    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

    authors: Yoshiji H,Noguchi R,Ikenaka Y,Kaji K,Aihara Y,Shirai Y,Yoshii J,Yanase K,Fukui H

    更新日期:2011-07-01 00:00:00

  • Comparative genomics on FGF16 orthologs.

    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:

    authors: Katoh Y,Katoh M

    更新日期:2005-11-01 00:00:00

  • The metabolic syndrome of omega3-depleted rats. IV. Intestinal phospholipid omega3 fatty acids.

    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

    authors: Hacquebard M,Portois L,Malaisse WJ,Carpentier YA

    更新日期:2009-12-01 00:00:00

  • Adipose‑derived stem cells overexpressing SK4 calcium‑activated potassium channel generate biological pacemakers.

    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

    authors: Yang M,Zhao Q,Zhao H,Yang A,Wang F,Wang X,Tang Y,Huang C

    更新日期:2019-12-01 00:00:00

  • Adenosine and the adenosine A2A receptor agonist, CGS21680, upregulate CD39 and CD73 expression through E2F-1 and CREB in regulatory T cells isolated from septic mice.

    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

    authors: Bao R,Shui X,Hou J,Li J,Deng X,Zhu X,Yang T

    更新日期:2016-09-01 00:00:00

  • Cardiomyopathy: molecular and immunological aspects (review).

    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:

    authors: Takeda N

    更新日期:2003-01-01 00:00:00

  • Involvement of the nuclear factor-κB signaling pathway in the regulation of CXC chemokine receptor-4 expression in neuroblastoma cells induced by tumor necrosis factor-α.

    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

    authors: Zhi Y,Lu H,Duan Y,Sun W,Guan G,Dong Q,Yang C

    更新日期:2015-02-01 00:00:00

  • Cloning of a rat-specific long PCP4/PEP19 isoform.

    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:

    authors: Sala A,Scaturro M,Proia P,Schiera G,Balistreri E,Aflalo-Rattenbach R,Créau N,Di Liegro I

    更新日期:2007-03-01 00:00:00

  • The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis.

    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

    authors: Chang J,Wang W,Zhang H,Hu Y,Wang M,Yin Z

    更新日期:2013-12-01 00:00:00