Periplocin Sensitizes Human Esophageal Squamous Cell Carcinoma to Trail-Induced Apoptosis via Upregulating Death Receptors and Inhibiting the Wnt/β-Catenin Pathway

2019 ◽  
Author(s):  
Lujuan Han ◽  
Suli Dai ◽  
Zhirong Li ◽  
Cong Zhang ◽  
Sisi Wei ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Death Receptors ◽  
Induced Apoptosis

scholarly journals Rps15a Imparts Chemoresistance by Regulating Cd44 Expression and Cell Stemness in Esophageal Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Pengjun Zhou ◽  
Xiaoping Wang ◽  
Ziyao Li ◽  
Yifei Wang ◽  
Rong Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Drug Efficacy ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Chemotherapeutic Drugs ◽  
Induced Apoptosis ◽  
Chemotherapy Efficacy

Abstract Chemotherapy is one of the effective ways to treat esophageal squamous cell carcinoma (ESCC), but the development of chemoresistance during chemotherapy lowers drug efficacy. Although previous studies have shown that the ribosomal protein S15A (RPS15A) involved in the progression and overall survival of malignancies, its function in chemoresistance is unknown. This study sought to elucidate the function of RPS15A in chemoresistance in ESCC. Our results show that knocking down or overexpressing RPS15A in ESCC cell lines can significantly change the sensitivity of chemotherapeutic drugs and affect cisplatin-induced apoptosis. Moreover, an increase in chemotherapeutic drug concentration leads to increased expression of RPS15A and CD44 proteins. When we utilized the ESCC cisplatin-resistant cell line to corroborate our findings, we found that the levels of RPS15A and CD44 proteins were substantially greater in daughter than parental cells. Subsequent experiments indicated that RPS15A modulated chemoresistance by controlling the expression of CD44 and the cell stemness in ESCC. Hence, our data suggest that RPS15A participates in the chemoresistance in ESCC by controlling the expression of CD44 and regulating cell stemness. Taken together, our study provides plausible mechanisms for RPS15A-mediated chemoresistance in ESCC cells and suggests that the inhibition of the RPS15A/CD44 pathway may be a potential target for improving chemotherapy efficacy.

scholarly journals Activation of PAR4 Upregulates p16 through Inhibition of DNMT1 and HDAC2 Expression via MAPK Signals in Esophageal Squamous Cell Carcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ming Wang ◽  
Shuhong An ◽  
Diyi Wang ◽  
Haizhen Ji ◽  
Xingjing Guo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Suppressor ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Dna Methyltransferase ◽  
Histone Deacetylase 2 ◽  
Erk Phosphorylation ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

A previous study showed that a downexpression of protease-activated receptor 4 (PAR4) is associated with the development of esophageal squamous cell carcinoma (ESCC). In this study, we explored the relationship between PAR4 activation and the expression of p16, and elucidated the underlying mechanisms in PAR4 inducing the tumor suppressor role in ESCC. ESCC cell lines (EC109 and TE-1) were treated with PAR4-activating peptide (PAR4-AP). Immunohistochemistry for DNA methyltransferase 1 (DNMT1) and histone deacetylase 2 (HDAC2) was performed in 26 cases of ESCC tissues. We found that DNMT1 and HDAC2 immunoreactivities in ESCC were significantly higher than those in adjacent noncancerous tissues. PAR4 activation could suppress DNMT1 and HDAC2, as well as increase p16 expressions, whereas silencing PAR4 dramatically increased HDAC2 and DNMT1, as well as reduced p16 expressions. Importantly, the chromatin immunoprecipitation-PCR (ChIP-PCR) data indicated that treatment of ESCC cells with PAR4-AP remarkably suppressed DNMT1 and HDAC2 enrichments on the p16 promoter. Furthermore, we demonstrated that activation of PAR4 resulted in an increase of p38/ERK phosphorylation and activators for p38/ERK enhanced the effect of PAR4 activation on HDAC2, DNMT1, and p16 expressions, whereas p38/ERK inhibitors reversed these effects. Moreover, we found that activation of PAR4 in ESCC cells significantly inhibited cell proliferation and induced apoptosis. These findings suggest that PAR4 plays a potential tumor suppressor role in ESCC cells and represents a potential therapeutic target of this disease.

STAT1 Activation-Induced Apoptosis of Esophageal Squamous Cell Carcinoma Cells In Vivo

2006 ◽  
Vol 14 (4) ◽  
pp. 1405-1415 ◽  
Author(s):  
Junichi Kaganoi ◽  
Go Watanabe ◽  
Michio Okabe ◽  
Shiro Nagatani ◽  
Atsushi Kawabe ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Induced Apoptosis

Resveratrol-induced apoptosis is enhanced by inhibition of autophagy in esophageal squamous cell carcinoma

2013 ◽  
Vol 336 (2) ◽  
pp. 325-337 ◽  
Author(s):  
Qishan Tang ◽  
Guanwu Li ◽  
Xiaoning Wei ◽  
Jun Zhang ◽  
Jen-Fu Chiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Induced Apoptosis

scholarly journals Apatinib induces endoplasmic reticulum stress-mediated apoptosis and autophagy and potentiates cell sensitivity to paclitaxel via the IRE-1α–AKT–mTOR pathway in esophageal squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Ming Wang ◽  
Xin Xu ◽  
Jian Tang ◽  
Zhi-Yong Sun ◽  
Yu-Jie Fu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endoplasmic Reticulum ◽  
Esophageal Squamous Cell Carcinoma ◽  
Er Stress ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Mtor Pathway ◽  
Induced Apoptosis

Abstract Background Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. Materials and methods The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. Results In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α–AKT–mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α–AKT–mTOR pathway. Conclusions Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α–AKT–mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies. Graphic abstract

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