XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway.

Abstract:

:Esophageal squamous cell carcinoma (ESCC) is a lethal disease due to its high aggressiveness. The aim of the present study was to investigate the role of xeroderma pigmentosum complementation group D (XPD) in the growth and invasion of ESCC and to elucidate the potential underlying molecular mechanisms. Western blot analysis and RT‑qPCR were used to detect the expression level of XPD in ESCC tissue samples and adjacent normal esophageal tissue samples. The pEGFP‑N2/XPD plasmid was transfected into human ESCC cell lines (EC9706 and EC109). The proliferation, apoptosis, migration and invasion of EC9706 or EC109 cells were assessed following transfection with the XPD overexpression plasmid. The chemosensitivity of EC9706 or EC109 cells to cisplatin or fluorouracil was evaluated by CCK‑8 assay. The expression levels of phosphoinositide 3‑kinase (PI3K)/AKT, nuclear factor (NF)‑κB, Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen‑activated protein kinase (MAPK) signaling pathway‑related genes were detected by RT‑qPCR and western blot analysis. The results demonstrated that the expression level of XPD was markedly lower in ESCC tissue samples than in adjacent normal esophageal tissue samples. The pEGFP‑N2/XPD plasmid was successfully transfected into EC9706 or EC109 cells, inducing XPD overexpression. A High XPD expression markedly suppressed cell proliferation, migration and invasion, and increased the apoptotic rate of EC9706 and EC109 cells. Furthermore, the overexpression of XPD significantly increased the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil. Following XPD overexpression, the expression levels of PI3K, p‑AKT, c‑Myc, Cyclin D1, Bcl‑2, vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)‑9 were markedly downregulated, while the expression level of p21 was markedly upregulated. On the whole, the findings of the present study demonstrate that XPD inhibits the growth and invasion of EC9706 and EC109 cells, whilst also enhancing the chemosensitivity of EC9706 and EC109 cells to cisplatin or fluorouracil by regulating the PI3K/AKT signaling pathway. XPD may thus be an underlying target for ESCC treatment and drug resistance.

journal_name

Int J Mol Med

authors

Jian J,Li S,Liu LZ,Zhen L,Yao L,Gan LH,Huang YQ,Fang N

doi

10.3892/ijmm.2020.4593

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

201-210

issue

1

eissn

1107-3756

issn

1791-244X

journal_volume

46

pub_type

杂志文章
  • Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity.

    abstract::Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance. The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function. The aim of the present study was t...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2475

    authors: Chen CC,Lee TY,Kwok CF,Hsu YP,Shih KC,Lin YJ,Ho LT

    更新日期:2016-03-01 00:00:00

  • Delayed angiogenesis in aging rats and therapeutic effect of adenoviral gene transfer of VEGF.

    abstract::We have studied an age-related impairment in angiogenesis and evaluated the effect of overexpressing VEGF in this situation. Polyvinyl alcohol sponges were implanted subcutaneously into aged (24-month), adult (12-month), and young (2-month) rats. Blood vessel ingrowth and proliferative activity in the sponges were ass...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Wang H,Keiser JA,Olszewski B,Rosebury W,Robertson A,Kovesdi I,Gordon D

    更新日期:2004-04-01 00:00:00

  • Enhanced rapamycin delivery to hemangiomas by lipid polymer nanoparticles coupled with anti-VEGFR antibody.

    abstract::The most common tumors in children are infantile hemangiomas which could cause morbidity and severe complications. The development of novel alternative drugs to treat infantile hemangiomas is necessary, since Hemangeol is the only US Food and Drug Administration-approved drug for infantile hemangiomas. However, Hemang...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3518

    authors: Li H,Teng Y,Xu X,Liu J

    更新日期:2018-06-01 00:00:00

  • Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells.

    abstract::Intermedin (IMD) is a recently discovered peptide closely related to adrenomedullin. Its principal physiological activity is its role in the regulation of the cardiovascular system, where it exerts a potent hypotensive effect. In addition, data were recently provided showing that this peptide is able to exert a clearc...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm_00000464

    authors: Albertin G,Sorato E,Oselladore B,Mascarin A,Tortorella C,Guidolin D

    更新日期:2010-08-01 00:00:00

  • Protective effects of CXCR3/HO‑1 gene‑modified BMMSCs on damaged intestinal epithelial cells: Role of the p38‑MAPK signaling pathway.

    abstract::The purpose of the present study was to investigate whether bone marrow mesenchymal stem cells (BMMSCs) modified by CXC‑chemokine receptor type 3 (CXCR3) and heme oxygenase‑1 (HO‑1) genes can repair damaged intestinal epithelial cells in vitro, and the role of the p38 mitogen‑activated protein kinase (p38‑MAPK) pathwa...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2019.4120

    authors: Yin M,Shen Z,Yang L,Zheng W,Song H

    更新日期:2019-05-01 00:00:00

  • TGF-β1 secreted by M2 phenotype macrophages enhances the stemness and migration of glioma cells via the SMAD2/3 signalling pathway.

    abstract::The positive correlation between the number of M2 phenotype TAMs (M2‑TAMs) and tumour development suggests a supportive role of M2‑TAMs in glioma progression. In the present study, the molecular link between glioma cells and M2‑TAMs was investigated and it was demonstrated that transforming growth factor‑β1 (TGF‑β1) s...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3923

    authors: Liu Z,Kuang W,Zhou Q,Zhang Y

    更新日期:2018-12-01 00:00:00

  • MicroRNA‑20b‑5p promotes ventricular remodeling by targeting the TGF‑β/Smad signaling pathway in a rat model of ischemia‑reperfusion injury.

    abstract::Myocardial ischemic injury results from severe impairment of the coronary blood supply and may lead to metabolic and ultrastructural changes, thereby causing irreversible damage. MicroRNA (miR)‑20b‑5p has been demonstrated to be involved in malignancies of the breast, colorectum, stomach, blood and oropharynx. The pre...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3695

    authors: Liang ZG,Yao H,Xie RS,Gong CL,Tian Y

    更新日期:2018-08-01 00:00:00

  • Cerebellin in the rat adrenal gland: gene expression and effects of CER and [des-Ser1]CER on the secretion and growth of cultured adrenocortical cells.

    abstract::Cerebellin (CER) is a regulatory peptide, originally isolated from rat cerebellum, which derives from the cleavage of precerebellin (Cbln), three types of which (Cbln1-3) have been identified in humans and rats. CER is also expressed in several extra-cerebellar tissues, including adrenal gland, and evidence has been p...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Rucinski M,Albertin G,Spinazzi R,Ziolkowska A,Nussdorfer GG,Malendowicz LK

    更新日期:2005-03-01 00:00:00

  • EZH2-mediated suppression of lncRNA-LET promotes cell apoptosis and inhibits the proliferation of post-burn skin fibroblasts.

    abstract::Although the upregulation of enhancer of zeste homolog 2 (EZH2) expression and downregulation of long non-coding RNA (lncRNA) LET expression are known to be associated with cell apoptosis and proliferation, little is known about the interaction of EZH2 with lncRNA LET. The present study aimed to investigate the intera...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2018.3425

    authors: Zheng W,Yu A

    更新日期:2018-04-01 00:00:00

  • Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome.

    abstract::Bloom syndrome (BS) is a rare genetic disorder characterized by small body size, photosensitivity, immunodeficiency and a high predisposition to various types of cancer. BLM was identified as the causative gene for BS. The BLM protein is homologous to DNA helicase and has two basic amino acid clusters in its C-termina...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.5.5.477

    authors: Hayakawa S,Kaneko H,Fukao T,Kasahara K,Matsumoto T,Furuichi Y,Kondo N

    更新日期:2000-05-01 00:00:00

  • Thrombospondin-1 induces apoptosis in primary leukemia and cell lines mediated by CD36 and Caspase-3.

    abstract::Thrombospondin-1 (TSP-1) is a naturally occurring anti-angiogenic compound that induces apoptosis of endothelial and cancer cells via its receptor CD36. The objectives of our study were to investigate the in vitro effects of TSP-1 on the apoptosis of primary human leukemia cells as well as leukemia cell lines and the ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Li K,Yang M,Yuen PM,Chik KW,Li CK,Shing MM,Lam HK,Fok TF

    更新日期:2003-12-01 00:00:00

  • Rosiglitazone attenuates atherosclerosis and increases high-density lipoprotein function in atherosclerotic rabbits.

    abstract::Rosiglitazone has been found to have anti-atherogenic effects and to increase serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels. However, in vivo studies investigating the regulation of adenosine triphosphate-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) by rosigli...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2015.2072

    authors: Li C,Tu Y,Liu TR,Guo ZG,Xie D,Zhong JK,Fan YZ,Lai WY

    更新日期:2015-03-01 00:00:00

  • Hypoxia enhances the wound-healing potential of adipose-derived stem cells in a novel human primary keratinocyte-based scratch assay.

    abstract::Preclinical studies have suggested that paracrine factors from adipose-derived stem cells (ASCs) promote the healing of chronic wounds, and that the exposure of ASCs to hypoxia enhances their wound healing effect. To aid the translation of these findings into clinical use, robust wound models are necessary to explore ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2017.2886

    authors: Riis S,Newman R,Ipek H,Andersen JI,Kuninger D,Boucher S,Vemuri MC,Pennisi CP,Zachar V,Fink T

    更新日期:2017-03-01 00:00:00

  • Effects of trichostatin A, a histone deacetylase inhibitor, on the regulation of apoptosis in H-ras-transformed breast epithelial cells.

    abstract::This study examined the mechanism for the anti-cancer effects of histone deacetylase (HDAC) inhibitor trichostatin A (TsA) in H-ras-transformed human breast epithelial (MCF10A-ras) cells. The effects of TsA on anti-cancer effects of MCF10A-ras cells were determined by measuring the level of cell cycle regulator expres...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Park H,Lee YJ,Kim TH,Lee J,Yoon S,Choi WS,Myung CS,Kim HS

    更新日期:2008-11-01 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

  • microRNAs and thyroid cancer: biological and clinical significance (Review).

    abstract::Despite recent advances in the management of thyroid cancer, the survival rate of this tumor may still be improved. Therefore, the identification of biological and molecular features of indolent and aggressive disease would be critical to define clinically useful predictors of high-...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章,评审

    doi:10.3892/ijmm.2012.1089

    authors: Leonardi GC,Candido S,Carbone M,Colaianni V,Garozzo SF,Cinà D,Libra M

    更新日期:2012-11-01 00:00:00

  • Oxidant-induced cardiomyocyte injury: identification of the cytoprotective effect of a dopamine 1 receptor agonist using a cell-based high-throughput assay.

    abstract::Myocyte injury due to myocardial reperfusion injury plays a crucial role in the pathogenesis of acute myocardial infarction even after successful coronary revascularization. Identification of compounds that reduce reperfusion-associated myocyte death is important. Therefore, we developed an in vitro model of myocardia...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Gerö D,Módis K,Nagy N,Szoleczky P,Tóth ZD,Dormán G,Szabó C

    更新日期:2007-11-01 00:00:00

  • Roles of SEA-expressing Staphylococcus aureus, isolated from an atopic dermatitis patient, on expressions of human beta-defensin-2 and inflammatory cytokines in HaCaT cells.

    abstract::Atopic dermatitis (AD) shows an increased susceptibility to Staphylococcus aureus infection partly due to decreased expression of human beta-defensin-2 (HBD-2). Interestingly, it was reported that the nasal carrier S. aureus down-regulates the expression of HBD-2 and -3, thereby the carrier strains of S. aureus retain...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm_00000135

    authors: Cho JW,Cho SY,Lee KS

    更新日期:2009-03-01 00:00:00

  • Aryl hydrocarbon receptor inhibits inflammation in DSS‑induced colitis via the MK2/p‑MK2/TTP pathway.

    abstract::The pathogenesis of inflammatory bowel disease (IBD) is believed to be associated with the abnormal expression of inflammatory factors. The aryl hydrocarbon receptor (AhR) is a ligand‑dependent transcription factor, which can suppress the inflammatory response and attenuate experimental colitis. However, the detailed ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2017.3262

    authors: Wang Q,Yang K,Han B,Sheng B,Yin J,Pu A,Li L,Sun L,Yu M,Qiu Y,Xiao W,Yang H

    更新日期:2018-02-01 00:00:00

  • Adrenomedullin is expressed in cord blood hematopoietic cells and stimulates their clonal growth.

    abstract::Adrenomedullin (AM) is a hypotensive peptide, which originates from the proteolytic cleavage of pro(p)AM and acts via AM22-52-sensitive receptors. Reverse transcription polymerase chain reaction allowed the detection of the specific mRNAs of pAM in the mononuclear hematopoietic cells of the cord blood and immunocytoch...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Del Pup L,Belloni AS,Carraro G,De Angeli S,Parnigotto PP,Nussdorfer GG

    更新日期:2003-02-01 00:00:00

  • Effect of the harvest procedure and tissue site on the osteogenic function of and gene expression in human mesenchymal stem cells.

    abstract::Evidence has indicated that mesenchymal stem cells (MSCs) harvested with the Reamer/Irrigator/Aspirator (RIA) procedure exhibited an improved osteogenic differentiation capability compared with MSCs obtained by bone marrow aspiration from the iliac crest. In the present study, we hypothesized that the harvest procedur...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2489

    authors: Henrich D,Nau C,Kraft SB,Zollfrank M,Kontradowitz K,Oppermann E,Schultheiss J,Meier S,Frank J,Marzi I,Seebach C

    更新日期:2016-04-01 00:00:00

  • Effects of a Rho kinase inhibitor on the sequential expression of ICAM-1, HIF-1α, Bcl-2 and caspase-3 in the retina of rats with oxygen-induced retinopathy.

    abstract::The aim of the present study was to evaluate the effects of blocking the Rho kinase pathway on non-perfused regions and angiogenesis in the retina of rats using a rat model of oxygen-induced retinopathy (OIR) by observing the sequential expression of intercellular adhesion molecule-1 (ICAM-1), hypoxia-inducible factor...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2013.1410

    authors: Wang H,Chen X

    更新日期:2013-08-01 00:00:00

  • Sequential fluctuation pattern of serum des-gamma-carboxy prothrombin levels detected by high-sensitive electrochemiluminescence system as an early predictive marker for hepatocellular carcinoma in patients with cirrhosis.

    abstract::Serum concentration levels of des-gamma-carboxy prothrombin (DCP), alpha-fetoprotein (AFP) and Lens culinaris agglutinin-reactive fraction (AFP-L3) are useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Recently, a novel immunoassay using the electrochemiluminescence (ECLIA) was developed to ena...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Shimizu A,Shiraki K,Ito T,Sugimoto K,Sakai T,Ohmori S,Murata K,Takase K,Tameda Y,Nakano T

    更新日期:2002-03-01 00:00:00

  • The metabolic syndrome of omega3-depleted rats. III. Brain phospholipids.

    abstract::Rats exposed from 7 weeks after birth and for the ensuing 3 to 7 months to a diet depleted in long-chain polyunsaturated omega3 fatty acids were recently proposed as a new animal model for the metabolic syndrome. The present study aimed mainly at investigating whether, in this new model, the perturbation of the fatty ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

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

    更新日期:2009-08-01 00:00:00

  • Mutational analysis of the DAL-1/4.1B tumour-suppressor gene locus in meningiomas.

    abstract::The DAL-1/41B gene (differentially expressed in adenocarcinoma of the lung), located in the chromosome 18p11.3 region, belongs to the protein family 4.1 (membrane-associated proteins), which includes the product of the NF2 gene (merlin), and the proteins, ezrin, radixin, and moesin. DAL-1/4.1B is normally expressed at...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Martinez-Glez V,Bello MJ,Franco-Hernandez C,De Campos JM,Isla A,Vaquero J,Rey JA

    更新日期:2005-10-01 00:00:00

  • Functional analysis of the nuclear localization signal of the POU transcription factor Skn‑1a in epidermal keratinocytes.

    abstract::POU domain proteins are a family of critical regulators of development and differentiation due to their transcriptional activity in the nucleus. Skn‑1a, a member of the POU domain protein family, appears to be expressed predominantly in epidermal keratinocytes and is thought to play a critical role in keratinocyte dif...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2014.1803

    authors: Moritsugu R,Tamai K,Nakano H,Aizu T,Nakajima K,Yamazaki T,Sawamura D

    更新日期:2014-08-01 00:00:00

  • Identification of LMX1B gene point mutations in italian patients affected with Nail-Patella syndrome.

    abstract::Nail-Patella syndrome, or osteo-onychodysplasia, is an autosomal dominant disorder characterized by nail dysplasia, absent or hypoplastic patellae, iliac horns and nephropathy. Previous studies have demonstrated linkage of the Nail-Patella locus with polymorphic markers on human chromosome 9q34. Recently, point mutati...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.4.3.285

    authors: Seri M,Melchionda S,Dreyer S,Marini M,Carella M,Cusano R,Piemontese MR,Caroli F,Silengo M,Zelante L,Romeo G,Ravazzolo R,Gasparini P,Lee B

    更新日期:1999-09-01 00:00:00

  • In silico-initiated cloning and molecular characterization of cortexin 3, a novel human gene specifically expressed in the kidney and brain, and well conserved in vertebrates.

    abstract::We report on the in silico-initiated cloning and molecular characterization of CTXN3 (cortexin 3), a new human gene that was specifically expressed in the kidney and brain due to tissue-specific alternative exon 1 usage, on chromosome 5q23.2 using digital gene expression displayer (DGED) and a novel in silico cloning ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Wang HT,Chang JW,Guo Z,Li BG

    更新日期:2007-10-01 00:00:00

  • Low vitamin D-modulated calcium-regulating proteins in psoriasis vulgaris plaques: S100A7 overexpression depends on joint involvement.

    abstract::Psoriasis is an inflammatory skin disease with or without joint involvement. In this disease, the thickened epidermis and impaired barrier are associated with altered calcium gradients. Calcium and vitamin D are known to play important roles in keratinocyte differentiation and bone metabolism. Intracellular calcium is...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:10.3892/ijmm.2016.2718

    authors: Cubillos S,Norgauer J

    更新日期:2016-10-01 00:00:00

  • Plasminogen activator inhibitor-1 is locked in active conformation and polymerizes upon binding ligands neutralizing its activity.

    abstract::Plasminogen activator inhibitor-1 (PAI-1), a member of the serpin super-family, forms a covalent complex with its target proteinases, such as tissue and urokinase plasminogen activators. Thus, PAI-1 controls the physiological and pathological proteolysis. An abnormal expression of PAI-1 has been observed in different ...

    journal_title:International journal of molecular medicine

    pub_type: 杂志文章

    doi:

    authors: Jankun J,Specht Z,Szkudlarek M,Greenfield R,Gaikwad B,Trifonov L,Vaugeois J,Aleem AM,Basrur V,Selman SH,Zavodszky MI,Skrzypczak-Jankun E

    更新日期:2006-03-01 00:00:00