Experimental and mathematical models of intracellular calcium dynamics for evaluating combined anticancer effects of Afatinib and RP4010 in esophageal cancer

Targeting dysregulated Ca2+ signaling in cancer cells is an emerging chemotherapy approach. We previously reported that store-operated Ca2+ entry (SOCE) blockers, such as RP4010, are promising antitumor drugs for esophageal cancer. As a tyrosine kinase inhibitor (TKI), afatinib received FDA approval to be used in targeted therapy for patients with EGFR mutation-positive cancers. While preclinical studies and clinical trials have shown that afatinib has benefits for esophageal cancer patients, it is not known whether combination of afatinib and RP4010 could achieve better anticancer effects. Since TKI can alter intracellular Ca2+ dynamics through EGFR/phospholipase C-γ pathway, in this study, we evaluated the inhibitory effect of afatinib and RP4010 on intracellular Ca2+ oscillations in esophageal cancer cells using both experimental and mathematical simulations. Our mathematical simulation of Ca2+ oscillations could fit well with experimental data responding to aftinib or RP4010, separately or in combination. The results showed that combination of afatinib and RP4010 presented synergistic anticancer effect. This intracellular Ca2+ dynamic-based mathematical simulation approach could be useful for a rapid and cost-effective evaluation of combined targeting therapy drugs.

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Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence

Molecules ◽

10.3390/molecules24061054 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1054 ◽

Cited By ~ 3

Author(s):

Jingxin Ma ◽

Xiaopeng Hu ◽

Chenghui Liao ◽

Haitao Xiao ◽

Qinchang Zhu ◽

...

Keyword(s):

Cell Cycle ◽

Esophageal Cancer ◽

Cell Cycle Arrest ◽

Cancer Cells ◽

Inhibitory Effect ◽

Cancer Cell Growth ◽

Therapeutic Drugs ◽

Cycle Arrest ◽

Chemical Inhibitors ◽

Esophageal Cancer Cells

Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy.

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The pan-erbB tyrosine kinase inhibitor CI-1033 inhibits human esophageal cancer cells in vitro and in vivo

Oncology Reports ◽

10.3892/or.17.4.887 ◽

2007 ◽

Cited By ~ 2

Author(s):

E. Ako ◽

Y. Yamashita ◽

M. Ohira ◽

M. Yamazaki ◽

T. Hori ◽

...

Keyword(s):

Esophageal Cancer ◽

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Cancer Cells ◽

Kinase Inhibitor ◽

Human Esophageal Cancer ◽

Esophageal Cancer Cells

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Mannose enhances the radio-sensitivity of esophageal squamous cell carcinoma with low MPI expression by suppressing glycolysis

Discover Oncology ◽

10.1007/s12672-021-00447-0 ◽

2022 ◽

Vol 13 (1) ◽

Author(s):

Hui Luo ◽

Xiaohui Wang ◽

Yunhan Wang ◽

Qinfu Dan ◽

Hong Ge

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Inhibitory Effect ◽

Esophageal Cancer Cell ◽

Human Esophageal Cancer ◽

Radio Sensitivity ◽

Esophageal Cancer Cells ◽

Kyse450 Cell

Abstract Background To investigate the effect of mannose on radio-sensitivity of human esophageal squamous cell carcinoma (ESCC) cell line and its possible mechanism. Methods The expression of mannose phosphate isomerase (MPI) in human esophageal cancer cell lines were detected by Western blot. The inhibitory effect of mannose on human esophageal cancer cell lines were observed by MTT assay. Plate clone formation assay was performed to investigate the efficacy of mannose on radio-sensitivity of human esophageal cancer cells. The apoptosis rates of tumor cells treated with mannose and/or radiation therapy was calculated by flow cytometry. Furthermore, we analyzed intracellular metabolites using liquid chromatography mass spectrometry to identify selective sugar metabolites. Results MPI expression was various in human esophageal cancer cells. KYSE70 cells was associated with the highest MPI expression whereas KYSE450 cells had the lowest MPI expression level. When administrated with 11.1 mM/L mannose, the same inhibitory effect was observed in both KYSE70 and KYSE450 cell lines. Moreover, the inhibitory effect was significant on KYSE450 cell lines with an increased mannose concentration. The application of 11.1 mM/L mannose could significantly enhance the radio-sensitivity of KYSE450 cell line; and tumor cell apoptosis rate was also increased. However, there was limited efficacy of mannose on the radio-sensitivity and apoptosis rate of KYSE70 cell line. Additionally, intracellular metabolites analyzation revealed that glycolysis could be disturbed by mannose when combined with radiation therapy in esophageal cancer cells. Conclusion In esophageal cancer cell lines with low MPI expression, the administration of mannose was associated with enhanced radio-sensitivity.

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A chalcone inhibits the growth and metastasis of KYSE-4 esophageal cancer cells

Journal of International Medical Research ◽

10.1177/0300060520928831 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052092883

Author(s):

Jie Chen ◽

Chun-Yan Kang ◽

Zhao-Xia Niu ◽

Hui-Cong Zhou ◽

Hong-Mei Yang

Keyword(s):

Esophageal Cancer ◽

Cell Growth ◽

Cancer Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Anticancer Effects ◽

Esophageal Cancer Cells

Objective To investigate the in vitro and in vivo anticancer effects of a chalcone against KYSE-4 esophageal cancer cells. Methods A chalcone was synthesized via the molecular hybridization strategy based on the anticancer activity of chalcone and dithiocarbamate scaffolds. The anticancer effects of different concentrations of the chalcone derivative were compared in esophageal cancer cells. Results This chalcone displayed strong inhibitory effects on esophageal cancer cell growth with an IC50 of 1.06 μM in KYSE-4 cells. Analysis of the mechanism revealed that the derivative obviously inhibited KYSE-4 cell growth, migration, and invasion in a concentration-dependent manner. Furthermore, the compound regulated migration-related biomarkers (E-cadherin, N-cadherin, and Slug) and inhibited the Wnt/β-catenin pathway. According to western blotting, this chalcone suppressed the expression of proline-rich protein 11 (PRR11) in a concentration- and time-dependent manner. Conclusions This chalcone might be a leading candidate for suppressing the growth and metastasis of esophageal cancer by downregulating PRR11 expression and inhibiting Wnt/β-catenin signaling.

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EMT Participates in the Regulation of Exosomes Secretion and Function in Esophageal Cancer Cells

Technology in Cancer Research & Treatment ◽

10.1177/15330338211033077 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110330

Author(s):

Chuangui Chen ◽

Zhao Ma ◽

Hongjing Jiang

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Promoting Effect ◽

Migration Ability ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

And Migration ◽

And Function ◽

Esophageal Cancer Cells

Epithelial-mesenchymal transition (EMT) is a key step in tumor invasion and distant metastasis. Abundant evidence has documented that exosomes can mediate EMT of tumor cells and endow them with the ability of invasion and migration. However, there are few studies focusing on whether EMT can reverse the secretion of exosomes. In this study, 2 esophageal cancer cells (FLO-1 and SK-GT-4) were selected to compare the migration ability and EMT activation, and to further analyze the secretion ability of exosomes of the 2 cell lines. According to the results, inhibited activation of EMT in FLO-1 cells with relatively high migration ability could effectively reduce the secretion of exosomes. Besides, in SK-GT-4 cells, EMT activation induced by TGF-β could promote the secretion of exosomes. FLO-1 cell derived exosomes exhibited a paracrine effect of promoting the migration of SK-GT-4 cells, and the use of EMT inhibitors could weaken this ability. Furthermore, inhibition of EMT could change the relative content of some miRNAs in exosomes, with a particularly significant downregulation in the expression of miR-196-5p, miR-21-5p and miR-194-5p. Significantly, artificial transfection of the 3 miRNAs into exosomes by electroporation resulted in the recovery of migration-promoting effect of exosomes. Subsequent experiments further revealed that the effect of EMT on these miRNAs could be explained by the intracellular transcription level or the specific sorting mechanism of exosomes. To sum up, our study undoubtedly reveals that EMT has a regulatory effect on exosomes in the quantity and contents in esophageal cancer cells. Significantly, findings in our study provide experimental evidence for the interaction of EMT with the secretion and sorting pathway of exosomes, and also give a new direction for the further study of tumor metastasis.

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Neddylation Inhibition Activates the Extrinsic Apoptosis Pathway through ATF4–CHOP–DR5 Axis in Human Esophageal Cancer Cells

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-15-2254 ◽

2016 ◽

Vol 22 (16) ◽

pp. 4145-4157 ◽

Cited By ~ 45

Author(s):

Ping Chen ◽

Tao Hu ◽

Yupei Liang ◽

Pei Li ◽

Xiaoyu Chen ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Apoptosis Pathway ◽

Extrinsic Apoptosis ◽

Human Esophageal Cancer ◽

Esophageal Cancer Cells

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Characteristics of P-Type and N-Type Photoelectrochemical Biosensors: A Case Study for Esophageal Cancer Detection

Nanomaterials ◽

10.3390/nano11051065 ◽

2021 ◽

Vol 11 (5) ◽

pp. 1065

Author(s):

Joseph-Hang Leung ◽

Hong-Thai Nguyen ◽

Shih-Wei Feng ◽

Sofya B. Artemkina ◽

Vladimir E. Fedorov ◽

...

Keyword(s):

Esophageal Cancer ◽

Cancer Cells ◽

Carrier Transport ◽

X Ray Diffraction ◽

Photoelectrochemical Response ◽

Carrier Separation ◽

Human Esophageal Cancer ◽

P Type ◽

Esophageal Cancer Cells

P-type and N-type photoelectrochemical (PEC) biosensors were established in the laboratory to discuss the correlation between characteristic substances and photoactive material properties through the photogenerated charge carrier transport mechanism. Four types of human esophageal cancer cells (ECCs) were analyzed without requiring additional bias voltage. Photoelectrical characteristics were examined by scanning electron microscopy (SEM), X-ray diffraction (XRD), UV–vis reflectance spectroscopy, and photocurrent response analyses. Results showed that smaller photocurrent was measured in cases with advanced cancer stages. Glutathione (L-glutathione reduced, GSH) and Glutathione disulfide (GSSG) in cancer cells carry out redox reactions during carrier separation, which changes the photocurrent. The sensor can identify ECC stages with a certain level of photoelectrochemical response. The detection error can be optimized by adjusting the number of cells, and the detection time of about 5 min allowed repeated measurement.

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