Apatinib affects the proliferation, migration and apoptosis of esophageal cancer cells both in vitro and in xenografts by regulating Ras/Raf/MEK/ERK and JAK2/STAT3 signaling pathways.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15501-e15501
Author(s):  
Jingping Yu
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Formation Rate ◽  
Xenograft Model ◽  
Control Group ◽  
Expression Levels ◽  
Esophageal Cancer Cells ◽  
Carcinoma Xenograft

e15501 Background: To investigate the effects of apatinib on esophageal cancer cells in vitro and xenograft models, and discuss the mechanisms of its actions. Methods: Used various assays to measure the different biological processes of esophageal cancer cells: used MTT assay to measure the proliferation rate; used transwell assay to determine the migration capacity and used colony formation assay to assess the clone formation rate. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression levels of VEGF and VEGFR2 were measured by qRT-PCR. The concentration of VEGF in the supernatant of cancer cell was assessed by ELISA. The expression levels of MEK, ERK, p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 after VEGF stimulation were detected by western blot. We also established human esophageal squamous carcinoma xenograft model in nude mice. The mice were randomly divided into healthy control group, low dose group (250mg) and high dose group (500mg), with 6 mice in each group. The tumor growth rate of each group was calculated, and the expression levels of VEGF and VEGFR2 in tumor tissues were detected by immunohistochemistry. Results: Apatinib inhibited the proliferation of esophageal cancer cell in a time-dependent (P < 0.05) and concentration-dependent (P < 0.05) manner; it also inhibited the cell migration capacity (P < 0.05) and colony formation rate (P < 0. 05). In addition, apatinib induced apoptosis in esophageal cancer cells and increased the proportion of cells in G2 / M phase (P < 0.05). The mRNA levels of VEGF (P < 0.05) and VEGFR2 (P < 0.05) and the protein levels of VEGF (P < 0.05) were also suppressed by apatinib. Western blot showed that apatinib could down-regulate the expression of p-MEK, p-ERK, STAT3, p-STAT3, CHK2 and CDC2 (P < 0.05). The inhibition rates of apatinib in esophageal carcinoma xenograft model was 29.25% and 19.96% for 250mg and 500mg drug treatment groups. Compared with healthy control group, the VEGF levels in drug treatment groups were not significantly different (P > 0.05), but the VEGFR2 levels were significantly decreased (P < 0.05). Conclusions: Apatinib can induce apoptosis of esophageal cancer cell KYSE-150 and ECA-109, and inhibit the cell proliferation, migration and colony formation. Moreover, apatinib can inhibit the tumor growth in esophageal carcinoma xenograft models. This inhibitory action of apatinib is related to the alterations in VEGF-related pathways such as Ras / Raf / MEK / ERK and JAK2 / STAT3 pathways.

scholarly journals EMT and Cancer Cell Stemness Associated With Chemotherapeutic Resistance in Esophageal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaojie Liu ◽  
Mingjing He ◽  
Linlin Li ◽  
Xiya Wang ◽  
Shuhua Han ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Cancer Drug ◽  
Drug Resistant ◽  
Esophageal Cancer Cells ◽  
Resistant Cells

Drug resistance often occurs after chemotherapy in esophageal cancer patients, leading to cancer metastasis and recurrence. However, the relationship among cancer cell migration, recurrence and drug resistance in esophageal cancer drug-resistant cells has not been clearly explained. In this study, we constructed paclitaxel (PTX)-resistant esophageal cancer cells to explore the causes of drug resistance and poor prognosis after chemotherapy in esophageal cancer. Colony formation assay was used to evaluate the difference of colony formation between parental cells and drug resistance cells. Microsphere formation assay was used to examine the phenotype of stem cells. Wound healing and Transwell assays were used to detect the migration ability of drug-resistant cells. Western blotting and immunofluorescence assays were used to explore the mechanisms. Finally, we used nude mouse xenograft model to explore the tumor characteristics and the expression of relative proteins to verify our findings in vivo. Our study demonstrated that the cancer cell stemness characteristics exist in drug-resistant esophageal cancer cells, that expressed the biomarkers of stem cells and were prone to epithelial-mesenchymal transition (EMT). Our results suggested that the expression of EMT biomarkers and stemness-related proteins increased in esophageal cancer cells after continuously using chemotherapeutic drugs for a period of time. This study indicated that simultaneously targeting EMT and stemness could be a better strategy for the treatment of esophageal cancer drug resistance.

scholarly journals Cordycepin enhances the chemosensitivity of esophageal cancer cells to cisplatin by inducing the activation of AMPK and suppressing the AKT signaling pathway

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Ying Gao ◽  
Dan-Lei Chen ◽  
Mi Zhou ◽  
Zhou-san Zheng ◽  
Mei-Fang He ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Expression Levels ◽  
In Vivo Animal Model ◽  
Esophageal Cancer Cells

Abstract Although cisplatin (cDDP), is a first-line chemotherapy drug for esophageal cancer, it still has the potential to develop drug resistance and side effects. There is increasing evidence that cordycepin can work synergistically with other chemotherapy drugs. Therefore, we investigated whether combination therapy of cordycepin and cDDP may enhance the therapeutic effect of cDDP. We performed a series of functional tests to study the effect of medical treatment on esophageal cancer cells. We then used GO analysis to examine the pathways affected by treatment with cordycepin and cDDP. Next, we observed changes in the abundance of the selected pathway proteins. The in vivo animal model supported the results of the in vitro experiments. Co-treatment with cordycepin and cDDP inhibited cell growth, migration, and metastasis, as well as induced apoptosis. Cordycepin was found to effectively enhance activation of AMPK and inhibited activity of AKT. In all treatment groups, the expression levels of p-PI3K, p-Akt, p-p70S6K, Caspase-3, and Bcl-2 were significantly reduced, while the expression levels of p-AMPK, cleaved Caspase-3, and Bax increased, and the total levels of Akt, PI3K, and p70S6K levels remained unchanged. Overall, cordycepin was found to enhance the chemical sensitivity of esophageal cancer cells to cisplatin by inducing AMPK activation and inhibiting the AKT signaling pathway. Combination therapy of cordycepin and cisplatin represent a novel potential treatment of esophageal cancer.

Oncolytic adenovirus expressing apoptotic genes targets radiation resistant (RR) esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21043-21043
Author(s):  
J. Y. Chang ◽  
R. Komaki ◽  
X. Zhang ◽  
L. Wang ◽  
B. Fang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Radiation Exposure ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Esophageal Cancer Cell ◽  
Esophageal Cancer Cells ◽  
Trans Gene ◽  
Fractionated Radiation

21043 Background: Only 25% of esophageal cancer patients achieve pathological complete response after standard chemoradiotherapy. Radiation dose escalation is associated with higher toxicity but no therapeutic improvement. In addition, esophageal cancer cells may develop radiation resistance (RR) after fractionated radiation exposure. Therefore, molecular targeting therapy for RR esophageal cancer is urgently needed. Methods: Six pairs of RR esophageal cancer cell lines were established by applying continuous 2 Gy fractionated irradiation. Ad/TRAIL-E1, an oncolytic adenoviral vector expressing both apoptotic TRAIL and viral E1A genes under the control of tumor specific human telomerase reverse transcriptase promoter, was constructed. Phosphate buffer solution and vectors expressing the TRAIL gene only, the GFP marker protein only, or the E1A gene only served as controls. Trans-gene expression, apoptosis activation, and the RR esophageal cancer cells targeted were evaluated in vitro and in vivo. A human esophageal RR cancer model was established and locally treated with Ad/TRAIL-E1 or controls. Results: After fractionated radiation exposure, esophageal cancer cell lines developed RR (up to 25-fold) that was associated with activation of the anti-apoptotic pathway. Ad/TRAIL-E1 activated an apoptotic cascade of caspases and selectively killed esophageal cancer cells but not normal cells. Ad/TRAIL-E1 preferentially targeted RR stem-like cancer cells with higher trans-gene expression and cell killing compared with parental cells. Overexpression (3 times) of Coxsackie's and adenoviral receptors in RR esophageal cancer cells compared with parental cells was noted. Ad/TRAIL-E1 therapy resulted in 40% tumor-free survival without the treatment- related toxicity found in human RR esophageal adenocarcinoma mouse models (p<0.05 as compared with controls). Conclusions: Esophageal cancer cells develop RR after fractionated radiation exposure. Ad/TRAIL-E1 preferentially targeted RR stem-like esophageal cancer cells, which resulted in a 40% cure rate. No significant financial relationships to disclose.

scholarly journals Study On the Antitumor Bioactivity of Koningic Acid in Thyroid Cancer in Vivo and in Vitro

2021 ◽  
Author(s):  
Changxin Jing ◽  
Yanyan Li ◽  
Zhifei Gao ◽  
Peng Hou ◽  
Rong Wang
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Colony Formation ◽  
Control Group ◽  
Dependent Manner ◽  
Thyroid Cancer Cell ◽  
Xenograft Tumor ◽  
Antitumor Effects ◽  
Thyroid Cancer Cells

Abstract Purpose: Koningic acid (KA), a sesquiterpene lactone, has been identified as an antimicrobial agent. Recent studies have revealed KA’s antitumor activities in colorectal cancer, leukemia, and lung cancer. However, its antitumor effect in thyroid cancer remains largely unknown. The aim of this study is to test the therapeutic potential of KA in thyroid cancer and explore the mechanisms underlying antitumor effects.Methods: We examined the effects of KA on proliferation, colony formation, apoptosis, ATP deprivation, and xenograft tumor growth in thyroid cancer cells.Results: KA inhibited thyroid cancer cell proliferation, colony formation, and induced cell apoptosis in a dose and time-dependent manner. Our data also showed that KA caused a rapid, extensive decrease of ATP levels in thyroid cancer cells. Growth of xenograft tumor derived from the thyroid cancer cell line C643 in nude mice was significantly inhibited by KA. Importantly, KA treatment did not cause significant liver and kidney damage in mice compared with the control group.Conclusion: KA may be used as an effective and safe agent for thyroid cancer treatment.

Inhibition of Growth of Esophageal Cancer by Alantolactone via Wnt/βCatenin Signaling

2021 ◽  
Vol 21 ◽  
Author(s):  
Zijie Wang ◽  
Qing Hu ◽  
Huan Chen ◽  
Lei Shi ◽  
Min He ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Xenograft Model ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Colony Formation Assay ◽  
Crystal Violet Assay ◽  
Murine Xenograft Model ◽  
Anti Cancer ◽  
Esophageal Cancer Cells

Background: Alantolactone (AL) is a natural compound extracted from the roots of Inula Helenium L, which exerts an antitumor effect in a variety of cancer cell lines; however, its effect on esophageal cancer, a common malignancy with poor prognosis, remains unclear. Therefore, we aim to evaluate the effect of AL on esophageal cancer and to explore its underlying mechanism. Objective: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism. Objective: This study aims to determine whether AL has an anti-cancer effect on esophageal cancer cells and to explore its underlying mechanism. Methods: The effect of AL on the proliferation and apoptosis of esophageal cancer cells was detected by MTT assay, colony formation assay, crystal violet assay, flow cytometry and hoechst apoptosis staining. The wound healing and Transwell invasion assay were performed to examine the effect of AL on the migration and invasion of esophageal cancer cells. Luciferase reporter system and Western blot were used to study the anti-tumor mechanism of AL on esophageal cancer cells. The subcutaneous murine xenograft model was employed to verify the effects of AL on esophageal cancer cells . Results: MTT assay, colony formation assay and crystal violet assay found that AL inhibited the growth of esophageal cancer cells. Hoechst staining and flow cytometry analysis showed that AL induced apoptosis in esophageal cancer through mitochondrial pathway. Transwell assay and wound healing assays showed that AL inhibited the metastasis and invasion of esophageal cancer cells. Wnt/ βcatenin signaling may contribute to the mechanism of the inhibition. The anti-tumor effect of AL on esophageal cancer cells was validated on murine xenograft model. Conclusion: Our data indicate that AL inhibits proliferation, migration, and invasion of esophageal cancer cells, and promotes apoptosis of esophageal cancer cells through the Wnt/β-catenin signaling pathway.

scholarly journals Qigesan Reduced the Migration and Invasion of Esophageal Cancer Cells via Inhibiting TGF-β1 Pathway

2021 ◽  
Author(s):  
Yin-wan Shang ◽  
Rui Zhu ◽  
Dan-hua Meng ◽  
Ying-shuo Wu ◽  
Xing Chen ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Control Group ◽  
Group Model ◽  
Mesenchymal Transition ◽  
Gene And Protein Expression ◽  
Esophageal Cancer Cells ◽  
Tgf Β1 ◽  
E Cadherin

Abstract Background: The present study aim to investigate the mechanism of Qigesan (QGS) on migration and invasion of esophageal cancer cells. Methods: First, we detected the cells in the normal group and the QGS group using microarray, and analyzed the ontology function and signaling pathway of target genes, and screened out TGF-β as one of the important targets of QGS. The subsequent verification experiments were divided into four groups: control group, model group (TGF-β1 stimulation group), QGS group (TGF-β1+QGS group) and positive control group (TGF-β1+TGF-β1 receptor inhibitor group). The migration and invasion abilities, as well as the expressions of related proteins and mRNA of each experimental group were detected. The migration and invasion ability of cells were detected by cell scratch test, and the Gene expression levels of E-cadherin, Vimentin, Smad2 and Smad7 mRNA in TGF-β1/Smad pathway were detected by RT-qPCR. The expression of E-cadherin, Vimentin, p-Smad2/3, Smad2/3 and Smad7 were detected by WB. Results: The results showed that TE-1 cells were reversed from fibroblast induced by TGF-β1 to epithelial cells after being treated QGS with the concentration of 20ug/mL for 36 h. Besides, QGS inhibited the migration and invasion of TE-1 cells and down-regulated the Gene and protein expression of Vimentin, Smad2 mRNA and Vimentin, p-Smad2/3 and Smad2/3. Meanwhile, The gene and protein overexpression E-cadherin and Smad7 was observed in QGS-treated cells. Conclusions: Together, these data indicated that QGS interfered with the epithelial-mesenchymal transition (EMT) process of TE-1 cells and reduced the migration and invasion of TE-1 cells via regulating TGF-β pathway, which maybe provided idea for the treatment of esophageal cancer.

scholarly journals Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Md Sazzad Hassan ◽  
Nicholas Cwidak ◽  
Chloe Johnson ◽  
Silvio Däster ◽  
Serenella Eppenberger-Castori ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Cdk Inhibitor ◽  
Xenograft Tumor ◽  
Subcutaneous Xenograft ◽  
Esophageal Cancer Cell ◽  
Esophageal Cancer Cells ◽  
Xenograft Tumor Growth

Tumors with elevated c-Myc expression often exhibit a highly aggressive phenotype, and c-Myc amplification has been shown to be frequent in esophageal cancer. Emerging data suggests that synthetic lethal interactions between c-Myc pathway activation and small molecules inhibition involved in cell cycle signaling can be therapeutically exploited to preferentially kill tumor cells. We therefore investigated whether exploiting elevated c-Myc expression is effective in treating esophageal cancer with the CDK inhibitor flavopiridol. We found frequent overexpression of c-Myc in human esophageal cancer cell lines and tissues. c-Myc overexpression correlated with accelerated esophageal cancer subcutaneous xenograft tumor growth. Esophageal cancer cells with elevated c-Myc expression were found preferentially more sensitive to induction of apoptosis by the CDK inhibition flavopiridol compared to esophageal cancer cells with lower c-Myc expression. In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.

scholarly journals Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF-κB/HIF-1α/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo

2018 ◽  
Vol 48 (5) ◽  
pp. 2035-2045 ◽  
Author(s):  
Yanjing Li ◽  
Hong Sui ◽  
Cailing Jiang ◽  
Shumin Li ◽  
Yu Han ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Photodynamic Therapy ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combined Treatment ◽  
Control Group ◽  
Vegf Pathway ◽  
Esophageal Cancer Cells

Background/Aims: Although photodynamic therapy (PDT) can relieve esophageal obstruction and prolong survival time of patients with esophageal cancer, it can induce nuclear factor-kappa B (NF-κB) activation in many cancers, which plays a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin derivative, can enhance the effect of PDT on esophageal cancer cells. However, the mechanism is still unclear. Methods: We generated stable cell lines expressing the super-repressor form of the NF-κB inhibitor IκBα and cell lines with lentivirus vector-mediated silencing of the HIF-1α gene. Esophageal xenograft tumors were created by subcutaneous injection of Eca109 cells into BALB/c nude mice. Four treatment groups were analyzed: a control group, photosensitizer alone group, light alone group, and PDT group. NF-κB expression was detected by an electrophoretic mobility shift assay, hypoxia-inducible factor α (HIF-1α) and vascular endothelial growth factor (VEGF) by real-time PCR, NF-κB, HIF-1α, and VEGF protein by western blot, and Ki-67, HIF-1α, VEGF, and NF-κB protein by immunohistochemistry. Results: PDT increased NF-κB activity and the gene expression of HIF-1α and VEGF in vitro and in vivo. In contrast, the DHA groups, particularly the combined DHA and PDT treatment group, abolished the effect. The combined treatment significantly inhibited tumor growth in vitro and in vivo. NF-κB activity and HIF-1α expression were also reduced in the stable IκBα expression group, whereas the former showed no change in HIF-1α-silenced cells. Conclusion: DHA might increase the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway.

scholarly journals Bax/Bcl-2 expression levels of 2-methoxyestradiol-exposed esophageal cancer cells

2005 ◽  
Vol 26 (3) ◽  
pp. 131-134 ◽  
Author(s):  
Annie JOUBERT ◽  
Christine MARITZ ◽  
Fourie JOUBERT
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Expression Levels ◽  
Esophageal Cancer Cells
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