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Even though nasopharyngeal carcinoma (NPC) is not common worldwide, it is a major public health burden in endemic areas. Distant metastasis often leads to a poor prognosis for NPC; therefore, new and effective anticancer strategies are needed. Ginkgolic acid (GA) is small-molecule compound existing in Ginkgo biloba that has various biologically relevant activities, including antitumor properties; however, its effects and mechanism of action in NPC are unknown. The effects of GA on NPC and such underlying mechanisms were investigated using 5-8F and CNE2 cells and NP69 human immortalized nasopharyngeal epithelial cells in this study. Moreover, the xenograft models were built to examine GA's effection in vivo. GA treatment decreased the survival and invasive capacity of 5-8F and CNE2 and induced their apoptosis, which varied with dose; this was accompanied by downregulation of B cell lymphoma (Bcl)2, upregulation of Bcl2-associated X protein, and activation of poly-ADP ribose polymerase, and caspase-9/-3. G0/G1 phase arrest was induced by GA in NPCs. It also reduced the expression of cyclin-dependent kinase 6 and its regulators cyclin D2 and cyclin D3. GA inhibited the activation of protein kinase B/nuclear factor signaling; this effect was potentiated with GA and 5-fluorouracil (5-FU), which also enhanced 5-FU-induced apoptosis. In summary, GA may be effective as an adjuvant to conventional chemotherapy drugs in preventing the progression of NPC.

Background: The PI3K signaling pathway has important roles in nasopharyngeal carcinoma (NPC) tumorigenesis and progression. Inhibition of the PI3K pathway effectively inhibits NPC growth; however, the toxic side effects of PI3K inhibitors limit their clinical application. This study aimed to investigate the effects of the selective PI3K p110β inhibitor, KIN-193, on proliferation and apoptosis in NPC. Methods: Cell counting Kit-8, colony formation, flow cytometry, and western blotting experiments were conducted in CNE2Z NPC cells treated with various concentrations of KIN-193 to determine its effects on cell proliferation and apoptosis. Additionally, xenograft tumor models were established in nude mice and the anti-tumor effects of KIN-193 and the classical P110α inhibitor, PIK-75, compared in vivo . Hematoxylin- eosin (HE) staining, immunohistochemical staining, and western blotting were also conducted to detect the protein expression levels of proliferation and apoptosis markers. Results: The results of both in vivo and in vitro experiments demonstrated that KIN-193 can dramatically inhibit cell proliferation and promote apoptosis in NPC. In addition, KIN-193 showed stronger antitumor effects, with fewer side effects, than PIK-75 in vivo . Conclusions: We conclude that KIN-193 exhibits considerable anti-tumor effects in NPC.

Even though nasopharyngeal carcinoma (NPC) is not common worldwide, it is a major public health burden in endemic areas. Distant metastasis often leads to a poor prognosis for NPC; therefore, new and effective anticancer strategies are needed. Ginkgolic acid (GA) is small-molecule compound existing in

Programmed death‑ligand 1 (PD‑L1), an immune co‑stimulatory molecule, is expressed on various cancer cells and the surface of immune cells. Its overexpression on tumor cells suppresses the immune response to promote tumor cell immune escape. The present study demonstrated that PD‑L1 was critical in head and neck squamous cell carcinoma (HNSCC) carcinogenesis. Immunohistochemical analysis of HNSCC tissue microarrays revealed that PD‑L1 was overexpressed in tumor tissue, and its expression increased as tumor malignancy progressed (from grade I to IV). Subsequently, the expression of PD‑L1 was knocked down or overexpressed in the HNSCC cell lines Cal‑27 and Fadu. It was demonstrated that PD‑L1 significantly induced HNSCC cell proliferation and colony forming ability. Cell proliferation was also promoted in Cal‑27 cell xenograft BALB/c nude mice. In addition, it was determined by western blotting that the PD‑L1‑mediated increase in HNSCC cell proliferation may have been associated with the activation of mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, mTOR inhibitor (rapamycin) prevented the increase in proliferation. Based on these results, it was concluded that PD‑L1 promoted cell proliferation of HNSCC cells through mTOR signaling, and blocking PD‑L1 may be conducive in HNSCC therapy.

Background: S100A14 is involved in multiple pathological processes; however, its role in nasopharyngeal carcinoma is poorly understood. Methods: S100A14 was deleted or upregulated in 6-10B cells. Results: S100A14-knockdown 6-10B cells showed significantly higher optical density values in the CCK-8 assay, smaller scratch width in the scratch experiment, and significantly more invading cells in the transwell assay compared with controls. Compared with the control group, the G2/M and S phase proportions of the S100A14-overexpression group were significantly higher, early apoptosis was observed via JC-1 fluorescence, and flow cytometry showed a significantly higher proportion of apoptotic cells. Protein expression of Bcl-2 and Bcl-xl decreased significantly, whereas that of Bax, Bad, cleaved-PARP, and cleaved-caspase-3/9 increased. Conclusions: Knockdown of S100A14 promoted proliferation, migration, and invasion of 6-10B cells, whereas its upregulation promoted caspase-dependent apoptosis and induced S and G2/M phase arrest, indicating a role of S100A14 as a tumor suppressor gene in nasopharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world, yet current treatment options are associated with limited success. The aim of the present study was to investigate the expression of ferritin in HNSCC and clarify whether it may serve as a biomarker for predicting HNSCC metastasis. The chemiluminescent immunoassay method was used to investigate the differences in the serum ferritin (SF) levels between patients with and without tumors, and between HNSCC with and without lymph node metastasis. The iron content and expression levels of ferritin were detected to verify the differences between tumor and normal tissues, and between HNSCC without and with lymph node metastasis. Data from the Gene Expression Omnibus (GEO) dataset was used to support the aforementioned results. No statistically significant difference in the SF level was observed between patients with and without tumors. Iron content and expression levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were higher in tumor tissues compared with normal tissues. The iron content and expression levels of SF, FTH and FTL were increased in HNSCC with metastasis compared with HNSCC without metastasis. The GEO dataset further verified the results and reported that the expression level of FTH was correlated with the prognosis of patients with HNSCC. Ferritin may not be a biomarker for the early diagnosis of HNSCC. However, an association exists between the expression level of ferritin and HNSCC cervical metastasis. SF may be a potential biomarker for predicting cervical lymph node metastasis in patients with HNSCC.

Head and neck cancer (HNC) is the sixth most common cancer worldwide. Recent studies on the pathogenesis of HNC have identified some biochemical associations of this disease, but the molecular mechanisms are not clear. To explore the genetic alterations in head and neck tumors, to identify new high-specificity and high-sensitivity tumor markers, and to investigate potentially effective therapeutic targets, in silico methods were used to study HNC. The {"type":"entrez-geo","attrs":{"text":"GSE58911","term_id":"58911"}}GSE58911 microarray dataset was downloaded from the Gene Expression Omnibus online database to identify potential target genes in the carcinogenesis and progression of HNC. Differentially expressed genes (DEGs) were identified and functional enrichment analysis was performed. In addition, a protein-protein interaction network was also constructed, and gene analysis was undertaken using Search Tool for the Retrieval of Interacting Genes and Cytoscape. A total of 648 differentially expressed genes were identified. Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology functional enrichment analysis of DEGs included muscle system process, extracellular matrix organization, actin binding, structural molecule activity, structural constituent of muscle, extracellular region part, ECM-receptor interaction, amoebiasis, focal adhesion, drug metabolism-cytochrome P450, and chemical carcinogenesis. There were 26 hub genes identified and biological process analysis revealed that these genes were mainly enriched in extracellular matrix organization, serine-type endopeptidase activity, extracellular matrix, and complement and coagulation cascades. Survival analysis revealed that interleukin (IL)-8 (C-X-C motif chemokine ligand 8), IL1B, and serpin family A member 1 may be involved in the carcinogenesis of HNC. In summary, the DEGs and hub genes identified in the present study may increase understanding of the molecular mechanisms of development of HNC and provide potential target genes for clinical diagnosis and targeted therapy.

Regional metastasis is an important prognostic factor for patients with head and neck squamous cell carcinoma (HNSCC). Neuromedin U (Nmu) is a secreted neuropeptide, named due to its potent uterine contraction‑inducing activity. The aim of the present study was to analyze the significance of Nmu in the regional metastasis of HNSCC. The characteristics of 240 patients recruited from the Department of Otolaryngology Head and Neck Surgery, Renmin Hospital of Wuhan University (Wuhan, China) were summarized retrospectively. The positive rate of neck dissection was analyzed according to the material. The expression levels of Nmu in human tumor samples were analyzed using immunohistochemistry. Subsequently, the expression of Nmu was investigated using a tissue microassay to analyze the association between Nmu protein expression and Tumor Node Metastasis (TNM) status. The positive rate of neck dissection was 51.4% in the study sample. The expression levels of Nmu in primary tumors with regional metastasis were higher, compared with those without metastasis. There was increased protein expression of Nmu in the advanced tumor tissues. The data obtained in the present study demonstrated that the expression of Nmu was correlated with regional metastasis and TNM status. Overexpression of Nmu may be involved in the process of regional metastasis of HNSCC, and may serve as a novel and valuable biomarker for predicting regional metastasis in patients with HNSCC.

The present study aimed to investigate the antitumor efficacy of di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) and di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) on head and neck squamous cell carcinoma (HNSCC) cells. The proliferation and apoptosis of HNSCC cells treated with the iron chelators DpC and Dp44mT were detected. The mechanism of DpC-induced apoptosis on HNSCC cells was investigated. The human HNSCC cell lines FaDu, Cal-27 and SCC-9 were cultured in vitro and exposed to gradient concentrations of DpC and Dp44mT. A Cell Counting Kit-8 assay was used to detect the viability of FaDu, Cal-27, SCC-9 cells. Double staining with annexin V and propidium iodide was performed for the detection of the proportion of apoptotic FaDu, Cal-27 and SCC-9 cells following treatment. The nuclear damage to Cal-27 cells that were treated with DpC was detected by Hoechst staining. Finally, western blot analysis was used to detect the expression of proteins associated with the DNA damage pathway in Cal-27 cells that were treated with DpC. The CCK-8 assay showed that treatment with DpC and Dp44mT was able to markedly inhibit the viability of FaDu, Cal-27 and SCC-9 cells in a concentration-dependent manner. In comparison to Dp44mT, treatment with DpC exhibited a more effective inhibitory effect on the viability of HNSCC cells. The proportion of apoptotic cells detected by flow cytometry increased in a dose-dependent manner in all cell lines following DpC and Dp44mT treatment, with the proportion of apoptotic HNSCC cells induced by DpC treatment being significantly higher compared with Dp44mT (P

Tobacco smoking was one of the risk factors for upper aerodigestive tract cancer, but exclusive quantification of the impact of cigarette smoking on laryngeal cancer had not been investigated. A meta-analysis of researches that had reported quantitative estimates of cigarette smoking and risk of laryngeal cancer by March 2016 was performed. Pooled estimates of relative risks and their 95% confidence intervals were obtained and summarized. Sensitivity analysis and subgroup analysis were implemented to find out sources of research heterogeneity and the effect of potential confounders. Publication bias was investigated and corrected if found to be present through Egger’s and Begg’s test, and trim and fill algorithm. Thirty researches based on a total of 14,292 cases from three cohort and fifteen case–control studies were included and pooled estimate for the correlation between cigarette smoking and the risk of laryngeal cancer was 7.01 (95% confidence interval 5.56–8.85), with moderate heterogeneity across the researches (I 2 = 56.7%, p = 0.002). The RRs were 5.04 (95% CI 3.09–8.22) for cohort studies (p = 0.121), 7.59 (95% CI 5.86–9.82) for case–control studies (p = 0.005). The risk kept elevated within the first fifteen years of quitting smoking(RR 3.62, 95% CI 1.88–7.00) but dropped in the 16 years and more after smoking cessation(RR 1.88, 95% CI 1.16–3.05). Individuals who smoked with 40 or more pack-years had nine times the risk of laryngeal cancer(RR 9.14; 95% CI 6.24–13.39). Subjects who smoked 30 or more cigarettes a day had sevenfolds the risk of laryngeal cancer (RR 7.02; 95% CI 4.47–11.02) and who smoked 40 or more years had five times the risk versus never smokers (RR 5.76; 95% CI 3.69–8.99). Evidence of publication bias was not detected for the correlation between current cigarette smoking and risk of laryngeal cancer (p = 0.225 with Begg’s test, p = 0.317 with Egger’s test). The results demonstrated strong correlation referring to dose–response and time–response between cigarette smoking and risk of laryngeal cancer for both men and women. The probability of developing laryngeal cancer was decreased by quitting smoking, particularly among former cigarette smokers who had stopped smoking for 15 or more years. The subgroup analysis demonstrated that study type influenced the RRs estimates of the studies.

Calpains are a family of intracellular cysteine proteases involved in various biological processes. Previously, the family was identified to have abnormal expression in several types of malignant tumor. Calpain 6 was less well known; however, it was recently identified to be involved in the carcinogenesis of certain types of malignant tumor. However, the expression of calpain 6 in head and neck squamous cell carcinoma (HNSCC) remains unclear. A total of six datasets from the Gene Expression Omnibus (GEO) was analyzed and an association between calpain 6 expression levels and HNSCC was identified, with the expression of calpain 6 observed to be significantly decreased in HNSCC (P