Human Nasopharyngeal Cells Research Articles

The association between infectious agents and breast cancer: a review of the epidemiologic evidence.

Several viruses have been casually linked to human cancers, including cervical, nasopharyngeal, liver, sarcoma, and Merkel cell carcinomas. However, the etiologic contribution of viral infections to breast cancer, the number one incident cancer among women worldwide, is not well established. Among studies exploring associations of viruses with breast cancer, potential linkages have been identified between breast cancer and five viruses: beta retrovirus, (i.e., mouse mammary tumor virus), human papillomavirus, Epstein Barr virus. bovine leukemia virus, and human cytomegalovirus. In this review, we provide a comprehensive evaluation of epidemiological ecologic, case-control, case-only, and cohort studies investigating these associations. Wediscuss results from several existing reviews and meta-analyses, evaluate epidemiological studies published in the past five years, and assess the relationship between these viruses and breast tumor clinicopathological factors. The strongest epidemiological evidence for a viral role in breast cancer exists for MMTV and HPV, though limitations include lack of prospective studies for MMTV and potential detection bias in HPV studies. Viral detection challenges have limited studies of EBV and HCMV. Fewer studies have evaluated BLV, and though it has been associated with higher risk of breast cancer, sample sizes are quite small. CONCLUSION: While epidemiologic evidence exists for an association between these five viruses and breast cancer, various methodological issues and lack of prospective studies preclude robustconclusions. Future research should prioritize establishing a temporal relationship between infection and disease, minimizing misclassification of detection assays, and further exploring the influence of co-infections.

Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae

AimsTo investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization. Methods and resultsGenomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose. ConclusionsPneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.

Lipoteichoic Acids Are Essential for Pneumococcal Colonization and Membrane Integrity.

The hydrophilic, polymeric chain of the lipoteichoic acid (LTA) of the Gram-positive pathobiont Streptococcus pneumoniae is covalently linked to the glycosylglycerolipid α-<sc>d</sc>-glucopyranosyl-(1,3)-diacylglycerol by the LTA ligase TacL, leading to its fixation in the cytoplasmic membrane. Pneumococcal LTA, sharing identical repeating units with the wall teichoic acids (WTA), is dispensable for normal growth but required for full virulence in invasive infections. Mutants deficient in TacL and complemented strains constructed were tested for their growth, resistance against oxidative stress, and susceptibility against antimicrobial peptides. Further, the membrane fluidity of pneumococci, their capability to adhere to lung epithelial cells, and virulence in a Galleria mellonella as well as intranasal mouse infection model were assessed. In the present study, we indicate that LTA is already indispensable for pneumococcal adherence to human nasopharyngeal cells and colonization in an intranasal mouse infection model. Mutants deficient for TacL did not show morphological defects. However, our analysis of pneumococcal membranes in different serotypes showed an altered membrane fluidity and surface protein abundance of lipoproteins in mutants deficient for LTA but not WTA. These mutants had a decreased membrane fluidity, exhibited higher amounts of lipoproteins, and showed an increased susceptibility to antimicrobial peptides. In complemented mutant strains, this defect was fully restored. Taken together, LTA is crucial for colonization and required to effectively protect pneumococci from innate immune defence mechanisms by maintaining the membrane integrity.

Detection and Monitoring of Circulating Tumor HPV DNA in HPV-Associated Sinonasal and Nasopharyngeal Cancers

This prospective observational study examines if circulating tumor human papillomavirus DNA can be used as an accurate measure of disease status at the time of diagnosis, throughout treatment, and during monitoring in human papillomavirus-associated sinonasal and nasopharyngeal squamous cell carcinomas.

Fluorescence lifetime imaging of water-soluble porphyrin in human nasopharyngeal cells under two-photon excitation

A comparative study of the two-photon absorption and emission properties of two free-based porphyrins (H2TMPyP and H2TPPS) and their zinc(II) complexes (ZnTMPyP and ZnTPPS) in three polar solvents has been carried out. The presence of the central zinc(II) ion leads to smaller two-photon absorption cross sections (δTPA), while the introduction of methylpyridinium substituents (N•+–CH3) results in larger ones. The δTPA values of H2TMPyP and ZnTMPyP are affected by both the solvent polarity and the hydrogen bonding between porphyrin and solvent molecules. In this work, the strongest two-photon fluorescence is given by H2TMPyP, which may efficiently get into four kinds of nasopharyngeal cell lines (NP69, SUNE1, CNE2, and CNE1) and prefer to localize in the nucleus. Two-photon fluorescence lifetime images of all the cell lines treated with H2TMPyP consist of a short- (τ1) and a long-lived component (τ2). The τ2 distribution of normal cell line NP69 shows one peak lifetime (∼2.12 ns), while those of the cancerous cell lines (SUNE1, CNE2, and CNE1) have two peak lifetimes (∼2.14 and ∼3.77 ns). The τ1 distribution around 0.68 ns is higher for the well differentiated nasopharyngeal cancerous cell line CNE1 compared with the poorly differentiated ones (SUNE1 and CNE2).

Latent Membrane Protein 1 (LMP1) from Epstein-Barr Virus (EBV) Strains M81 and B95.8 Modulate miRNA Expression When Expressed in Immortalized Human Nasopharyngeal Cells.

The Epstein–Barr virus (EBV) is a ubiquitous γ herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ in cell tropism and the activation of the lytic cycle. Nonetheless, it is unknown whether LMP1 from these strains have different effects when expressed in nasopharyngeal cells. Thus, herein we evaluated the effects of EBV LMP1 derived from viral strains B95.8 and M81 and expressed in immortalized nasopharyngeal cells NP69SV40T in the regulation of 91 selected cellular miRNAs. We found that cells expressing either LMP1 behave similarly in terms of NF-kB activation and cell migration. Nonetheless, the miRs 100-5p, 192-5p, and 574-3p were expressed at higher levels in cells expressing LMP1 B95.8 compared to M81. Additionally, results generated by in silico pathway enrichment analysis indicated that LMP1 M81 distinctly regulate genes involved in cell cycle (i.e., RB1), mRNA processing (i.e., NUP50), and mitochondrial biogenesis (i.e., ATF2). In conclusion, LMP1 M81 was found to distinctively regulate miRs 100-5p, 192-5p, and 574-3p, and the in silico analysis provided valuable clues to dissect the molecular effects of EBV LMP1 expressed in nasopharyngeal cells.

Isolation and Cell Culture of Human Nasopharyngeal Cells: A Model for Testing Immune Response and Antiviral Treatment.

The use of in vitro methods of infecting cell lines to test new treatments for SARS-CoV-2 does not always recapitulate the real context of the infection, and mouse models for SARS-CoV-2 infection are limited. Here we describe a novel ex vivo approach by collecting, isolating, and culturing nasal epithelial cells obtained from patients with COVID-19. This technique allows us to study immune responses and test new treatments directly on cells from patients naturally infected with SARS-CoV-2.

Potential of unglycosylated horseradish peroxidase variants for enzyme prodrug cancer therapy

Fighting cancer still relies on chemo- and radiation therapy, which is a trade-off between effective clearance of malignant cells and severe side effects on healthy tissue. Targeted cancer treatment on the other hand is a promising and refined strategy with less systemic interference. The enzyme horseradish peroxidase (HRP) exhibits cytotoxic effects on cancer cells in combination with indole-3-acetic acid (IAA). However, the plant-derived enzyme is out of bounds for medical purposes due to its foreign glycosylation pattern and resulting rapid clearance and immunogenicity. In this study, we generated recombinant, unglycosylated HRP variants in Escherichia coli using random mutagenesis and investigated their biochemical properties and suitability for cancer treatment. The cytotoxicity of the HRP-IAA enzyme prodrug system was assessed in vitro with HCT-116 human colon, FaDu human nasopharyngeal squamous cell carcinoma and murine colon adenocarcinoma cells (MC38). Extensive cytotoxicity was shown in all three cancer cell lines: the cell viability of HCT-116 and MC38 cells treated with HRP-IAA was below 1% after 24 h incubation and the surviving fraction of FaDu cells was ≤ 10% after 72 h. However, no cytotoxic effect was observed upon in vivo intratumoral application of HRP-IAA on a MC38 tumor model in C57BL/6J mice. However, we expect that targeting of HRP to the tumor by conjugation to specific antibodies or antibody fragments will reduce HRP clearance and thereby enhance therapy efficacy.

Oridonin inhibits epithelial-mesenchymal transition of human nasopharyngeal carcinoma cells by negatively regulating AKT/STAT3 signaling pathway.

Oridonin, derived from Rabdosia rubescens, has exhibited anticancer activity in a variety of cancers. However, few studies have explored the effect of oridonin (ORI) on migration, invasion and epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma. In our study, the results demonstrated that oridonin significantly inhibited migration and invasion of human nasopharyngeal carcinoma CNE-2Z and HNE-1 cell lines, as depicted by wound healing and Transwell assays. In addition, oridonin increased the expression of E-Cadherin while decreased the expressions of vimentin and twist1 at the mRNA and protein levels in a dose-dependent manner. Interestingly, oridonin also decreased cell mobility in nasopharyngeal carcinoma. The subsequent results of western blotting uncovered that the phosphorylation levels of AKT and signal transducer and activator of transcription 3 (STAT3) were decreased upon oridonin treatment. Furthermore, co-treatment with the AKT activator SC-79 attenuated the anti-metastatic effect of oridonin on nasopharyngeal carcinoma and partially abolished the high expression of E-cadherin and the low expression of twist1 mediated by oridonin. In conclusion, the results revealed that oridonin could repress metastatic phenotype and reverse epithelial-mesenchymal transition (EMT) in nasopharyngeal carcinoma by negatively regulating AKT/STAT3 signaling pathway, suggesting that AKT/STAT3 signaling may be the potential therapeutic target of oridonin against nasopharyngeal carcinoma.

Morusin Suppresses Cancer Cell Invasion and MMP-2 Expression through ERK Signaling in Human Nasopharyngeal Carcinoma.

The most important cause of treatment failure of nasopharyngeal carcinoma (NPC) patients is metastasis, including regional lymph nodes or distant metastasis, resulting in a poor prognosis and challenges for treatment. In the present study, we investigated the in vitro anti- tumoral properties of morusin on human nasopharyngeal carcinoma HONE-1, NPC-39, and NPC-BM cells. Our study revealed that morusin suppressed the migration and invasion abilities of the three NPC cells. Gelatin zymography assay and Western blotting demonstrated that the enzyme activity and the level of matrix metalloproteinases-2 (MMP-2) protein were downregulated by the treatment of morusin. Mitogen-activated protein kinase proteins were examined to identify the signaling pathway, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of morusin. In summary, our data showed that morusin inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by downregulating the ERK1/2 signaling pathway, suggesting that morusin may be a potential candidate for chemoprevention or adjuvant therapy of NPC.

MiR-34c downregulation leads to SOX4 overexpression and cisplatin resistance in nasopharyngeal carcinoma

BackgroundA major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance.MethodsTwo hundred forty-six NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666–1, were used for miR-34c gain-of-function and loss-of-function experiments. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay.ResultsMiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro. The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients.ConclusionmiR-34c is downregulated in NPC. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.

Evaluation of the effect of 5-aminolevulinic acid hexyl ester (H-ALA) PDT on EBV LMP1 protein expression in human nasopharyngeal cells.

Nasopharyngeal carcinoma (NPC) is of high prevalence in Hong Kong and southern China. The pathogenesis of NPC is closely associated with Epstein-Barr virus (EBV) infection via regulation of viral oncoprotein latent membrane protein 1 (LMP1). The conventional treatment for NPC is chemo-radiotherapy, but the prognosis remains poor for advanced stage, recurrent and metastatic NPC. Photodynamic therapy (PDT) is a therapeutic approach to combat tumors. PDT effectiveness depends on the interaction of photosensitizers, light and molecular oxygen. 5- aminolevulinic acid hexyl derivative (H-ALA) is one of the photosensitizers derived from 5-ALA. H-ALA with improved lipophilic properties by adding a long lipophilic chain (hexyl group) to 5-ALA, resulted in better penetration into cell cytoplasm. In this study, the effect of H-ALA-PDT on NPC cells (EBV positive C666-1 and EBV negative CNE2) was investigated. The H-ALA mediated cellular uptake and cytotoxicity was revealed via flow cytometry analysis and MTT assay respectively. H-ALA PDT mediated protein modulation was analysed by western blot analysis. Our finding reported that the cellular uptake of H-ALA in C666-1 and CNE2 cells was in a time dependent manner. H-ALA PDT was effective to C666-1 and CNE2 cells. EBV LMP1 proteins was expressed in C666-1 cells only and its expression was responsive to H-ALA PDT in a dose dependent manner. This work revealed the potential of H-ALA PDT as a treatment regiment for EBV positive NPC cells. Understanding the mechanism of H-ALA mediated PDT could develop improved strategies for the treatment of NPC.

Nondestructive quantification of single-cell nuclear and cytoplasmic mechanical properties based on large whole-cell deformation.

The mechanical properties of cell nuclei have been recognized to reflect and modulate important cell behaviors such as migration and cancer cell malignant tendency. However, these nuclear properties are difficult to characterize accurately using conventional measurement methods, which are often based on probing or deforming local sites over a nuclear region. The corresponding results are sensitive to the measurement position, and they are not decoupled from the cytoplasmic properties. Microfluidics is widely recognized as a promising technique for bioassay and phenotyping. In this report, we develop a simple and nondestructive approach for the single-cell quantification of nuclear elasticity based on microfluidics by considering different deformation levels of a live cell captured along a confining microchannel. We apply two inlet pressure levels to drive the flow of human nasopharyngeal epithelial cells (NP460) and human nasopharyngeal cancerous cells (NPC43) into the microchannels. A model considering the essential intracellular components (cytoplasm and nucleus) for describing the mechanics of a cell deforming along the confining microchannel is used to back-calculate the cytoplasmic and nuclear properties. On the other hand, we also apply a widely used chemical nucleus extraction technique to examine its possible effects (e.g., reduced nuclear modulus and reduced lamin A/C expression). To determine if the decoupled nuclear properties are representative of cancer-related attributes, we classify the NP460 and NPC43 cells using the decoupled physical properties as classification factors, resulting in an accuracy of 79.1% and a cell-type specificity exceeding 74%. It should be mentioned that the cells can be recollected at the device outlet after the nondestructive measurement. Hence, the reported cell elasticity measurement can be combined with downstream genetic and biochemical assays for general cell research and cancer diagnostic applications.

Folate-Targeted mRNA Delivery Using Chitosan-Functionalized Selenium Nanoparticles: Potential in Cancer Immunotherapy.

Systemic messenger RNA (mRNA) delivery, although still in its infancy, holds immense potential for application in cancer vaccination and immunotherapy. Its advantages over DNA transfection make it attractive in applications where transient expression is desired. However, this has proved challenging due to mRNA’s instability and susceptibility to degradation. Selenium is important for immune function and modulation, with selenium nanoparticles (SeNPs) finding a niche in biomedicine as drug delivery vehicles, owing to their biocompatibility, low toxicity, and biodegradability. In this investigation, we synthesized chitosan-coated SeNPs with a folic acid targeting moiety for Fluc mRNA delivery to cancer cells in vitro. Synthesized SeNPs were stable and well dispersed, and ranged from 59 to 102 nm in size. Nanoparticles bound and protected mRNA from RNase degradation, while exhibiting low cytotoxicity in the human embryonic kidney (HEK293), breast adenocarcinoma (MCF-7), and nasopharyngeal (KB) cells in culture. Moderate cytotoxicity evidenced in the colorectal carcinoma (Caco-2) and colon carcinoma (HT-29) cells was attributed to apoptosis induction by selenium, as confirmed by acridine orange/ethidium bromide staining. Selenium uptake studies corroborated the transfection results, where significant transgene expression was evident for the overexpressed folate receptor-positive KB cells when compared to the other cells with less or no folate receptors.

The CRISPR/Cas system in Neisseria meningitidis affects bacterial adhesion to human nasopharyngeal epithelial cells

ABSTRACTNeisseria meningitidis, a commensal β-proteobacterium of the human nasopharynx, constitutes a worldwide leading cause of sepsis and epidemic meningitis. A recent genome-wide association study suggested an association of its type II-C CRISPR/Cas system with carriage and thus less invasive lineages. Here, we show that knock-out strains lacking the Cas9 protein are impaired in the adhesion to human nasopharyngeal cells which constitutes a central step in the pathogenesis of invasive meningococcal disease. Transcriptome sequencing data further suggest that meningococcal Cas9 does not affect the expression of surface adhesins but rather exerts its effect on cell adhesion in an indirect manner. Consequently, we speculate that the meningococcal CRISPR/Cas system exerts novel functions beyond its established role in defence against foreign DNA.

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria).

Lanyamycin (1/2), a secondary metabolite occurring as two epimers, was isolated from the myxobacterium Sorangium cellulosum, strain Soce 481. The structures of both epimers were elucidated from HRESIMS and 1D and 2D NMR data and the relative configuration of their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929 and the human nasopharyngeal cell line KB3 with IC50 values of 3.1 and 1.5 μM, respectively, and also suppressed the growth of the Gram-positive bacterium Micrococcus luteus.

Quantitative analysis of γ-H2AX foci formation and dynamic changes in DNA double-strand breaks induced by X-ray radiation

Objective To quantitatively compare the γ-H2AX foci formation between DNA-PKcs+ /+ and DNA-PKcs-/-mouse embryonic fibroblast (MEF) cells, and to investigate the dynamic changes in DNA double-strand breaks (DSBs) in human nasopharyngeal carcinoma SUNE-1 cells exposed to X-ray radiation. Methods The expression of DNA-PKcs was determined by Western blot. The γ-H2AX foci formation induced by 5 Gy X-ray radiation was detected by cell immunofluorescence. The ImageJ software was used to quantitatively analyze the γ-H2AX foci formation. Results The expression of DNA-PKcs was silenced in DNA-PKcs-/-MEF cells and normal in DNA-PKcs+ /+ MEF cells. According to the dynamic analyses of the numbers of γ-H2AX foci/cell and γ-H2AX foci/mm2, a similar tendency was observed in DSB formation in DNA-PKcs+ /+ MEF cells, DNA-PKcs-/-MEF cells, and SUNE-1 cells exposed to X-ray radiation. A large number of γ-H2AX foci formed at 0.5-1.0 h after radiation. DSBs were repaired at 6 h after radiation in DNA-PKcs+ /+ MEF cells and 24 h after radiation in DNA-PKcs-/-MEF cells and SUNE-1 cells. The peak values of γ-H2AX foci/cell and γ-H2AX foci/mm2 were observed at 1.0 and 0.5 h after radiation, respectively. Compared with DNA-PKcs+ /+ MEF cells, DNA-PKcs-/-MEF cells had different numbers of γ-H2AX foci/cell at 0.5, 1.0, 3.0, 6.0, and 12.0 h after radiation, as well as different numbers of γ-H2AX foci/mm2 at 3.0, 6.0, and 12.0 h after radiation. Conclusions Quantitative measurement of the number of γ-H2AX foci/cell or γ-H2AX foci/mm2 by cell immunofluorescence provides new insights into the quantitative and dynamic study of DSB damage and repair. Key words: Non-homologous terminal connection; DNA dependent protein kinase catalytic subunit; γH2AX foci formation; SUNE-1 cell line

Induction of apoptosis by Streptomyces strain CH54-4 extract through activation of caspase-3 in human nasopharyngeal cells

Induction of apoptosis by Streptomyces strain CH54-4 extract through activation of caspase-3 in human nasopharyngeal cells

Effect of E1A gene on radiosensitivity of human nasopharyngeal carcinoma cells and its possible mechanism

Objective To investigate the effect of E1A gene on the radiosensitivity of human nasopharyngeal carcinoma cells and its possible mechanism. Methods The E1A gene was transfected into nasopharyngeal carcinoma CNE-2R cells by adenovirus vector. The expression of E1A gene was detected by RT-PCR. Untransfected CNE-2R cells (PBS group) and CNE-2R cells transfected with empty vector Ad-β-gal (Ad-β-gal group) and E1A (Ad-E1A group) were given 0 Gy, 2 Gy, 4 Gy, 6 Gy, 8 Gy 6 MV X-ray irradiation. The changes in radiosensitivity of CNE-2R cells were determined by colony-forming assay. Flow cytometry was used to analyze cell apoptosis in each group. The expression of NF-κB, CK2α, Bcl-2, and cleaved caspase-3 was measured by Western blot. Results RT-PCR confirmed that the E1A gene was transfected into CNE-2R cells and stably expressed. The Ad-E1A group had a significantly lower plating efficiency than the PBS group and the Ad-β-gal group (P<0.05). The Ad-E1A group had significantly lower cell survival rate at 2 Gy irradiation than the PBS group and the Ad-β-gal group (0.217 vs. 0.602, P<0.05; 0.217 vs. 0.585, P<0.05). The Ad-E1A group had a significantly higher α/β value than the PBS group and the Ad-β-gal group (24.680 vs. 5.268, P<0.05; 24.680 vs. 5.132, P<0.05). Flow cytometry results showed that irradiation alone could promote the apoptosis of CNE-2R cells, when combined with E1A gene, the apoptosis rate was significantly increased (P<0.05). Western blot results showed that E1A gene down-regulated the expression of NF-κB/p65, CK2α, and Bcl-2 and up-regulated the expression of cleaved caspase-3. Conclusions E1A gene can enhance the radiosensitivity of nasopharyngeal carcinoma cells by inhibiting the expression of CK2 to block the NF-κB signaling pathway and promoting cell apoptosis. Key words: E1A gene; NF-κB; Casein Kinase 2; Nasopharyngeal Carcinoma Cell; Radiosensitivity; Apoptosis

Inhibition of STAT1 sensitizes radioresistant nasopharyngeal carcinoma cell line CNE-2R to radiotherapy.

Radioresistance remains a major obstacle for clinicians in the treatment of nasopharyngeal carcinoma (NPC). Others and we have reported that signal transducer and activator of transcription 1 (STAT1) may be as an important gene for resistance to radiation. However, the relationship between STAT1 and radioresistance is still elusive. In this study, by constitutive silencing STAT1 in human radioresistant nasopharyngeal carcinoma CNE-2R cell line, we showed that inhibition of STAT1 enhanced radiosensitivity of CNE-2R. Furthermore, knockdown of STAT1 led to growth suppression and apoptosis promotion in vitro and in vivo. Moreover, cells with low STAT1 expression increased G2/M phase and decreased S phase at 2Gy. These result revealed that knockdown of stat1 expression could sensitizes the CNE-2R to radiotherapy, But the exact mechanism needs to be further clarified.