PS02.051: HMGB IS INVOLVED IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PROGRESSION

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 134-135
Author(s):  
Daiki Matsubara ◽  
Hirotaka Konishi ◽  
Katsutoshi Shoda ◽  
Tomohiro Arita ◽  
Toshiyuki Kosuga ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Healthy Volunteers ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Plasma Samples ◽  
Tissue Samples ◽  
Mrna And Protein Expression

Abstract Background High-mobility group box-1 (HMGB1), originally characterized as a non-histone, nuclear DNA-binding protein, acts as a crucial proinflammatory cytokine, mediating a broad range of inflammatory responses as a secretory form. Recently, it has been reported to be involved in the tumorigenesis and progression of various types of malignancies, but it is unclear whether HMGB1 plays an important role in the progression of esophageal squamous cell carcinoma (ESCC). The aim of this study was to investigate the significance of HMGB1 in ESCC. Methods The tissue and plasma samples were obtained from ESCC patients at before or after operative period and healthy volunteers. The ESCC cell lines and normal human cell lines, such as fibroblast (WI-38) or Human umbilical vein endothelial cell (HUVEC), were used in vitro analyses. The expression levels of HMGB1 in tissue samples were measured by quantitative RT-PCR. The protein levels of HMGB1 were measured using the HMGB1 enzyme-linked immunosorbent assay kit in plasma samples, and using immunohistochemical staining or western blotting in tissue samples or cell lines. The functions of HMGB1 on the ESCC cell lines were investigated by proliferation, invasion, or migration assays. Results The mRNA and protein expression of HMGB1 in ESCC tissue was significantly higher than that in paired non-cancerous esophageal mucosa tissue. Plasma HMGB1 level was slightly higher, but not significant, in ESCC patients than in healthy volunteers. However, it was significantly higher in ESCC patients with Neoadjuvant chemotherapy (NAC) than in those without NAC. The mRNA and protein expression of HMGB1 were higher in ESCC cell lines than in WI-38 or HUVEC. In ESCC cells with high HMGB1 expression, knockdown of HMGB1 using specific siRNAs inhibited the cell proliferation, migration and invasion. Conclusion These findings suggest that HMGB1 plays a crucial role in tumor malignant potential through its overexpression in esophageal squamous cell carcinoma. Disclosure All authors have declared no conflicts of interest.

scholarly journals CEP55 Positively Affects Tumorigenesis of Esophageal Squamous Cell Carcinoma and Is Correlated with Poor Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shu-Mei Yan ◽  
Lili Liu ◽  
Wan-Yi Gu ◽  
Li-Yun Huang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Colony Formation ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Mrna And Protein Expression ◽  
And Migration

Centrosomal protein 55 (CEP55) is a centrosome- and midbody-associated protein that is overexpressed in several cancers. However, the underlying molecular mechanism of CEP55-mediated progression and metastasis of esophageal squamous cell carcinoma (ESCC) is not clear. In the current study, we detected CEP55 mRNA by qRT-PCR while protein expression was detected by western blot analysis and immunohistochemistry (IHC). In addition, we knocked down CEP55 and investigated the ability of CEP55 to affect colony formation and migration. Here, we report that CEP55 mRNA and protein expression was significantly increased in ESCC. IHC staining showed that CEP55 expression correlated with TNM stage ( p = 0.046 ) and lymph node metastases ( p = 0.024 ). According to overall survival (OS) and disease-free survival (DFS), patients whose tumors expressed a higher level of CEP55 had a poorer prognosis than those with low expression level of CEP55. A multivariate analysis revealed that CEP55 expression was an independent prognostic indicator for patients with ESCC. Knockdown of CEP55 decreased the colony formation ability and migration of ESCC cells and also reduced the phosphorylation of Src, FAK, and ERK. Therefore, our study implied that CEP55 may be a valuable biomarker and a potential target in the treatment of patients with ESCC.

scholarly journals EGFR-IL-6 Signaling Axis Mediated the Inhibitory Effect of Methylseleninic Acid on Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Wang ◽  
Xianghe Liu ◽  
Guanghui Hu ◽  
Chenfei Hu ◽  
Yang Gao ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Cancer ◽  
Esophageal Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Inhibitory Effect ◽  
Esophageal Tumor ◽  
Methylseleninic Acid

Epidemiological and experimental evidence indicate that selenium is associated with a reduced risk of some cancers, including esophageal cancer. However, the exact mechanism is still unclear. In the present study, we used esophageal squamous cell carcinoma (ESCC) cell lines and animal models to explore the anti-cancer mechanism of methylseleninic acid (MSA). Firstly, MSA treatment dramatically attenuated Epidermal Growth Factor Receptor (EGFR) protein expression but did not alter mRNA levels in ESCC cells. On the contrary, EGFR overexpression partly abolished the inhibitory effect of MSA. With a microRNA-array, we found MSA up-regulated miR-146a which directly targeted EGFR, whereas miR-146a inhibitor antagonized MSA-induced decrease of EGFR protein. We further used 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumor mice model to evaluate the inhibitory effect of MSA in vivo. MSA treatment significantly decreased the tumor burden and EGFR protein expression in tumor specimens. Furthermore, MSA treatment inhibited EGFR pathway and subsequntly reduced Interleukin-6 (IL-6) secretion in the supernatant of cancer cell lines. MSA-induced IL-6 suppression was EGFR-dependent. To further evaluate the association of IL-6 and the anti-tumor effect of MSA on esophageal cancer, we established the 4NQO-induced esophageal tumor model in IL-6 knock-out (IL-6 KO) mice. The results showed that IL-6 deficiency did not affect esophageal tumorigenesis in mice, but the inhibitory effect of MSA was abolished in IL-6 KO mice. In conclusion, our study demonstrated that MSA upregulated miR-146a which directly targeted EGFR, and inhibited EGFR protein expression and pathway activity, subsequently decreased IL-6 secretion. The inhibitory effect of MSA on esophageal cancer was IL-6 dependent. These results suggested that MSA may serve as a potential drug treating esophageal cancer.

PS02.024: PRIMA-1 INDUCES P53-MEDIATED APOPTOSIS BY UPREGULATING NOXA IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH TP53 MISSENSE MUTATION

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 126-127
Author(s):  
Haruna Furukawa ◽  
Tomoki Makino ◽  
Makoto Yamasaki ◽  
Koji Tanaka ◽  
Yasuhiro Miyazaki ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Missense Mutation ◽  
Cell Lines ◽  
Squamous Cell ◽  
Antitumor Effect ◽  
Xenograft Model ◽  
Wild Type ◽  
Massive Apoptosis

Abstract Background TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore wild type activity to mutant p53 and induce massive p53-dependent apoptosis. APR-246 (methylated PRIMA-1) has been tested in a phase I/II clinical trial with promising results; however, the effects and mechanism in ESCC remain unknown. This study was designed to assess the antitumor effect of PRIMA-1 treatment in both ESCC cell lines with different TP53 status and an ESCC xenograft model and uncover the molecular mechanism of PRIMA-1. Methods After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1’s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo. Results PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with a TP53 missense mutation, whereas no apoptosis was induced in ESCC with wild type TP53 and with TP53 frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with a TP53 missense mutation. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation. Conclusion PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with a TP53 missense mutation. Disclosure All authors have declared no conflicts of interest.

scholarly journals Casticin treatment inhibits squamous cell carcinoma cell proliferation and arrests cell cycle in S phase

2016 ◽  
Vol 11 (1) ◽  
pp. 206 ◽  
Author(s):  
Yong-Bin Song ◽  
Shao-Hui Zhou ◽  
Hong-Shang Cui ◽  
Hui-Ning Liu ◽  
Li-Jun Liu
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines

<p class="Abstract">The present study demonstrates the effect of casticin on esophageal squamous cell carcinoma cell lines, TE-1 and TE-15. The cells were treated with various concentrations (10-50 μM) of casticin for different time periods. The results revealed that casticin treatment significantly inhibited the rate of cell proliferation in both TE-1 and TE-15 cell lines after 48 hours. Casticin treatment induced cell cycle arrest in S phase, enhanced the expression of proapoptotic gene, Bax and activation of caspase-3. Moreover, the morphological features of the cells were altered resulting in apoptosis. Casticin also inhibited the migration potential of TE-1 cells. Thus, casticin exhibits inhibitory effect on the esophageal squamous cell carcinoma cell lines by inhibiting cell proliferation, arresting cell cycle, inducing apoptosis and inhibiting migration. Therefore, casticin can be of therapeutic importance for the treatment of esophageal squamous cell carcinoma.</p><p> </p>

Sign in / Sign up

Export Citation Format

Share Document